medical-notes/content/Anatomi & Histologi 2/3 Öga histologi/24 Eye.md

# 24 EYE

**OVERVIEW OF THE EYE**

**GENERAL STRUCTURE OF THE EYE**


Layers of the Eye
Chambers of the Eye
Development of the Eye


**MICROSCOPIC STRUCTURE OF THE EYE**


Corneoscleral Coat

Vascular Coat (Uvea)

Retina

Crystalline Lens
Vitreous Body

**ACCESSORY STRUCTURES OF THE EYE**


**Folder 24.1** Clinical Correlation: Glaucoma

**Folder 24.2** Clinical Correlation: Retinal Detachment

**Folder 24.3** Clinical Correlation: Age-related Macular Degeneration
**Folder 24.4** Clinical Correlation: Clinical Imaging of the Retina
**Folder 24.5** Clinical Correlation: Color Blindness

**Folder 24.6** Clinical Correlation: Conjunctivitis


**HISTOLOGY**

### **OVERVIEW OF THE EYE**


The **eye** is a complex sensory organ that provides the sense of sight. In many
ways, the eye is similar to a digital camera. Like the optical system of a
camera, the **cornea** and **lens** of the eye capture and automatically focus light,
whereas the iris automatically adjusts the diameter of the pupil to differences
in illumination. The light detector in a digital camera, the charge-coupled
device (CCD), consists of closely spaced photodiodes that capture, collect, and
convert the light image into a series of electrical impulses. Similarly, the
**photoreceptor cells** in the **retina** of the eye detect light intensity and color
(wavelengths of visible light that are reflected by different objects) and encode
these parameters into electrical impulses for transmission to the brain via the
**optic nerve** . The retina has other capabilities beyond those of a CCD: It can
extract and modify specific impulses from the visual image before sending
them to the central nervous system (CNS).

In other ways, the optical system of the eye is far more elaborate and
complex than a camera. For example, the eye is able to track moving objects
with coordinated eye movements. The eye can also protect, maintain, selfrepair, and clean its transparent optical system.


Because the eyes are paired and spatially separated, two slightly different
and overlapping views (visual fields) are sent to the brain. The brain integrates
these two slightly different images from each eye into a single **three-**
**dimensional (3D) image** in a process called **stereopsis** . The primary visual
cortex located in the occipital lobes processes the differences between the two
images to create the perception of depth. The final image is then projected onto
the visual cortex. In addition, other complex neural mechanisms coordinate
eye movements, enabling refinements in the perception of depth and distance.
Therefore, the way in which we see the world around us largely depends on
impulses processed within the retina and the analysis and interpretation of
these impulses by the CNS.

### **GENERAL STRUCTURE OF THE EYE**


The eye measures approximately 25 mm in diameter. It is suspended in the
bony orbital socket by six extrinsic muscles that control its movement. A thick
layer of adipose tissue partially surrounds and cushions the eye as it moves
within the orbit. The extraocular muscles are coordinated so that the eyes
move symmetrically around their own central axes.

### **Layers of the Eye**


**The wall of the eye consists of three concentric layers or coats.**


The eyeball is composed of three concentric structural layers (Fig. 24.1):


**FIGURE 24.1.** **Schematic diagram of the layers of the eye.** The wall of the
eyeball is organized in three separate concentric layers: an outer supporting


fbrous layer, the corneoscleral coat; a middle vascular coat or uvea; and an i
inner layer consisting of the retina. Note that the retina has two layers: a neural
retina ( _yellow_ ) and a retinal pigment epithelium ( _orange_ ). The photosensitive
and nonphotosensitive parts of the neural retina occupy different regions of the
eye. The photosensitive part of the retina is found in the posterior part of the
eye and terminates anteriorly along the ora serrata. The nonphotosensitive
region of the retina is located anterior to the ora serrata and lines the inner
aspect of the ciliary body and the posterior surface of the iris. The vitreous body
( _partially removed_ ) occupies considerable space within the eyeball.


The **corneoscleral coat**, the outer or fibrous layer, includes the **sclera**, the
white portion, and the **cornea**, the transparent portion.
The **vascular coat**, the middle layer, or **uvea**, includes the **choroid** and
the stroma of the **ciliary body** and **iris** .
The **retina**, the inner layer, includes an outer pigment epithelium, the inner
neural retina, and the epithelium of the ciliary body and iris. The neural
retina is continuous with the CNS through the **optic nerve** .


**The corneoscleral coat consists of the transparent cornea and the**
**white opaque sclera.**


The **cornea** covers the anterior one-sixth of the eye (see Fig. 24.1). In this
window-like region, the surface of the eye has a prominence or convexity. The
cornea is continuous with the **sclera** _[Gr. skleros, hard]_ . The sclera is
composed of dense fibrous connective tissue that provides attachment for the
extrinsic muscles of the eye. The corneoscleral coat encloses the inner two
layers, except where it is penetrated by the optic nerve. The sclera
constitutes the “white” of the eye. In children, it has a slightly blue tint
because of its thinness; in elderly people, it is yellowish because of the
accumulation of lipofuscin in its stromal cells. A noticeable feature of
patients with **jaundice** is a yellow discoloration of the sclera ( **scleral**
**icterus** ) caused by a high level of circulating bilirubin.


**The uvea consists principally of the choroid, the vascular layer that**
**provides nutrients to the retina.**


Blood vessels and melanin pigment give the **choroid** an intense dark brown
color. The pigment absorbs scattered and reflected light to minimize glare
within the eye. The choroid contains numerous venous plexuses and layers of
capillaries and is firmly attached to the retina (see Fig. 24.1). The anterior rim
of the uveal layer continues forward, where it forms the stroma of the **ciliary**
**body** and **iris** .

The **ciliary body** is a ring-like thickening that extends inward just
posterior to the level of the corneoscleral junction. Within the ciliary body is
the **ciliary muscle**, a smooth muscle that is responsible for lens


**accommodation** . Contraction of the ciliary muscle changes the shape of the
lens, which enables it to bring light rays from different distances to focus on
the retina.

The **iris** is a contractile diaphragm that extends over the anterior surface of
the lens. It also contains smooth muscle and melanin-containing pigment cells
scattered in the connective tissue. The **pupil** is the central circular aperture of
the iris. It appears black because one looks through the lens toward the heavily
pigmented back of the eye. In the process of **adaptation**, the iris contracts or
expands, changing the size of the pupil in response to the amount of light that
passes through the lens to reach the retina.


**The retina consists of two components: the neural retina and pigment**
**epithelium.**


The **retina** is a thin, delicate layer (see Fig. 24.1) consisting of two
components:


The **neural retina** is the inner layer that contains light-sensitive receptors
and complex neuronal networks.
The **retinal pigment epithelium (RPE)** is the outer layer composed of
simple cuboidal melanin-containing cells.


Externally, the retina rests on the choroid; internally, it is associated with
the vitreous body. The neural retina consists largely of **photoreceptor cells**,
called retinal **rods** and **cones**, and interneurons. Visual information encoded
by the rods and cones is sent to the brain via impulses conveyed along the
optic nerve.

### **Chambers of the Eye**


**The layers of the eye and the lens serve as boundaries for three**
**chambers within the eye.**


The chambers of the eye are as follows:


The **anterior chamber** is the space between the cornea and the iris.
The **posterior chamber** is the space between the posterior surface of the
iris and the anterior surface of the lens.
The **vitreous chamber** is the space between the posterior surface of the
lens and the neural retina (Fig. 24.2). The cornea, the anterior and posterior
chambers, and their contents constitute the anterior segment of the eye. The
vitreous chamber, visual retina, RPE, posterior sclera, and uvea constitute
the posterior segment.


**FIGURE 24.2.** **Schematic diagram illustrating the internal structures of the**
**human eye.** This diagram shows the relationship between the layers of the eye
and internal structures. The lens is suspended between the edges of the ciliary
body. Note the posterior chamber of the eye, which is a narrow space between
the anterior surface of the lens and the posterior surface of the iris. It
communicates through the pupil with the larger anterior chamber that is
bordered by the iris and the cornea. These spaces are filled with the aqueous
humor produced by the ciliary body. The large cavity posterior to the lens, the
vitreous chamber, is filled with a transparent jelly-like substance called the
_vitreous body_ . In this figure, most of the vitreous body has been removed to
illustrate the distribution of the central retinal vessels on the surface of the
retina. The other layers of the eyeball and the attachment of two of the
extraocular muscles to the sclera are also shown.


**The refractile media components of the eye alter the light path to**
**focus it on the retina.**


As light rays pass through the components of the eye, they are refracted.
Refraction focuses the light rays on the photoreceptor cells of the retina. Four
transparent components of the eye, called the **refractile (or dioptric) media**,
alter the path of the light rays:


The **cornea** is the anterior window of the eye.


The **aqueous humor** is the watery fluid located in the anterior and
posterior chambers.
The **lens** is a transparent, crystalline, biconvex structure suspended from the
inner surface of the ciliary body by a ring of radially oriented fibers, the
**zonule of Zinn** .
The **vitreous body** is composed of a transparent gel-like substance that fills
the vitreous chamber. It acts as a “shock absorber” that protects the fragile
retina during rapid eye movement and helps maintain the shape of the eye.
The vitreous body is almost 99% water with soluble proteins, hyaluronan,
glycoproteins, widely dispersed collagen fibrils, and traces of other
insoluble proteins. The fluid component of the vitreous body is called the
**vitreous humor** .


The **cornea** is the chief refractive element of the eye. It is the single most
powerful focusing element of the eye and has a refractive index of 1.376 (air
has a refractive index of 1.0). The cornea provides about 80% of the eye’s
refractive power and is almost twice as powerful as the lens. The lens is
second in importance to the cornea in refracting light rays. It is responsible for
fine-tuning and focusing light onto the retina. Because of its elasticity, the
shape of the **lens** can undergo slight changes in response to the tension of the
ciliary muscle. These changes are important in **accommodation** for proper
focusing on near objects. The aqueous humor and vitreous body have only
minor roles in refraction. However, the aqueous humor plays an important role
in providing nutrients to two avascular structures, the lens and cornea. In
addition to transmitting light, the vitreous body helps maintain the position of
the lens and helps keep the neural retina in contact with the RPE.

### **Development of the Eye**


To appreciate the unusual structural and functional relationships in the eye, it
is helpful to understand how it forms in the embryo.


**The tissues of the eye are derived from neuroectoderm, surface**
**ectoderm, and mesoderm.**


By the 22nd day of development, the **eyes** are evident as shallow grooves—
the **optic sulci** or **optic grooves** —located in the neural folds at the cranial
end of the embryo. As the neural tube closes, the paired grooves form
outpocketings called **optic vesicles** (Fig. 24.3a). As each optic vesicle grows
laterally, the connection to the forebrain becomes constricted into an optic
stalk, and the overlying surface ectoderm thickens and forms a **lens placode** .
These events are followed by concomitant invagination of the optic vesicles
and the lens placodes. The invagination of the optic vesicle results in the
formation of a double-layered **optic cup** (Fig. 24.3b). The inner layer


becomes the **neural retina** . The outer layer becomes the **RPE** . The
mesenchyme surrounding the optic cup gives rise to the **sclera** .


**FIGURE 24.3.** **Schematic drawing illustrating the development of the eye.**
**a.** Forebrain and developing optic vesicles as seen in a 4-mm embryo. **b.**


Bilayered optic cup and invaginating lens vesicle as seen in a 7.5-mm embryo.
The optic stalk connects the developing eye to the brain. **c.** The eye as seen in
a 15-week fetus. All the layers of the eye are established, and the hyaloid
artery traverses the vitreous body from the optic disc to the posterior surface of
the lens.


Invagination of the central region of each **lens placode** results in the
formation of the **lens vesicle** . By the fifth week of development, the lens
vesicle loses contact with the surface ectoderm and comes to lie in the mouth
of the optic cup. After the lens vesicle detaches from the surface ectoderm, this
same site again thickens to form the corneal epithelium. **Mesenchymal cells**
from the periphery then give rise to the **corneal endothelium** and the
**corneal stroma** .

Grooves containing blood vessels derived from mesenchyme develop
along the inferior surface of each optic cup and stalk. Called the **choroid**
**fissures**, the grooves enable the hyaloid artery to reach the inner chamber of
the eye. This artery and its branches supply the inner chamber of the optic cup,
lens vesicle, and mesenchyme within the optic cup. The hyaloid vein returns
blood from these structures. The distal portions of the hyaloid vessels
degenerate, but the proximal portions remain as the **central retinal artery** and
**central retinal vein** . By the end of the seventh week, the edges of the choroid
fissure fuse, and a round opening, the future pupil, forms over the lens vesicle.

The **outer layer of the optic cup** forms a single layer of pigmented cells
(Fig. 24.3c). Pigmentation begins at the end of the fifth week. The **inner layer**
undergoes a complex differentiation into the nine layers of the **neural retina** .
The photoreceptor cells (rods and cones) as well as the bipolar, amacrine, and
ganglion cells and nerve fibers are present by the seventh month. The macular
depression, a future site of fovea centralis, begins to develop during the eighth
month and is not complete until about 6 months after birth.

During the third month, the growth of the optic cup gives rise to the **ciliary**
**body** and the future **iris**, which forms a double row of epithelium in front of
the lens. The mesoderm located external to this region becomes the stroma of
the ciliary body and iris. Both epithelial layers of the iris become pigmented.
In the ciliary body, however, only the outer layer is pigmented. At birth, the
iris is light blue in fair-skinned people because the pigment is usually not
present. The dilator and sphincter pupillary muscles develop during the sixth
month as derivatives of the neuroectoderm of the outer layer of the optic cup.

The embryonic origins of the individual eye structures are summarized in
Table 24.1.



**TABLE 24.1**



**Embryonic Origins of the Individual Structures of the**
**Eye**


**Source** **Derivative**



Surface


ectoderm


Neural


ectoderm



Lens
Epithelium of the cornea, conjunctiva, and lacrimal gland and

its drainage system


Vitreous body (derived partly from neural ectoderm of the optic

cup and partly from mesenchyme) Epithelium of the retina,
iris, and ciliary body Sphincter pupillae and dilator papillae
muscles Optic nerve



Mesoderm Sclera
Stroma of the cornea, ciliary body, iris, and choroids

Extraocular muscles
Eyelids (except epithelium and conjunctiva) Hyaloid system

(most of which degenerates before birth) Coverings of the
optic nerve Connective tissue and blood vessels of the eye,
bony orbit, and vitreous body

### **MICROSCOPIC STRUCTURE OF THE EYE**


The three layers of the eye—the **corneoscleral coat**, the **vascular coat**, and
the **retina** —are in turn composed of complex molecular layers and structures
that reflect their various functions.

### **Corneoscleral Coat**


The cornea is a unique tissue and the most powerful focusing element of the
eye. It forms part of the anterior segment of the eye, protecting structures
within the eye from the external environment. The most important
characteristics of the cornea include its mechanical strength and transparency
to incoming light.


**The cornea consists of five layers: three cellular layers and two**
**noncellular layers.**


The transparent **cornea** (see Figs. 24.1 and 24.2) is only 0.5 mm thick at its
center and about 1 mm thick peripherally. It consists of three cellular layers
that are distinct in both appearance and origin. These layers are separated by
two important membranes that appear homogeneous when viewed in the light
microscope. Thus, the **five layers of the cornea** seen in a transverse section
are the following:


**Corneal epithelium**
**Bowman membrane** (anterior basement membrane)
**Corneal stroma**


**Descemet membrane** (posterior basement membrane)
**Corneal endothelium**


**The corneal epithelium is a nonkeratinized stratified squamous**
**epithelium.**


The **corneal epithelium** (Fig. 24.4) represents **nonkeratinized stratified**
**squamous epithelium** that consists of approximately five layers of cells and
measures about 50 μm in average thickness. It is continuous with the
conjunctival epithelium that overlies the adjacent sclera. The epithelial cells
adhere to neighboring cells via desmosomes that are present in short
interdigitating processes. Like other stratified epithelia, such as that of the
skin, the cells proliferate from a basal layer and become squamous at the
surface. The basal cells are low columnar with round, ovoid nuclei; the surface
cells acquire a squamous or discoid shape, and their nuclei are flattened and
pyknotic (Fig. 24.4b). As the cells migrate to the surface, the cytoplasmic
organelles gradually disappear, indicating a progressive decline in metabolic
activity. The corneal epithelium has a remarkable regenerative capacity with a
turnover time of approximately 7 days.


**FIGURE 24.4.** **Photomicrograph of the cornea. a.** This photomicrograph of a
section through the full thickness of the cornea shows the corneal stroma and
the two corneal surfaces covered by different types of epithelia. The corneal
stroma does not contain blood or lymphatic vessels. ×140. **b.** A higher
magnification of the anterior surface of the cornea showing the _corneal stroma_
covered by a stratified squamous (corneal) _epithelium_ . The basal cells that rest
on _Bowman membrane_, which is a homogeneous condensed layer of corneal
stroma, are low columnar in contrast to the squamous surface cells. Note that


one of the surface cells is in the process of desquamation ( _arrow_ ). ×280. **c.** A
higher magnification photomicrograph of the posterior surface of the cornea
covered by a thin layer of simple squamous epithelium (corneal _endothelium_ ).
These cells are in direct contact with the aqueous humor of the anterior
chamber of the eye. Note the very thick _Descemet membrane_ (basal lamina) of
the corneal endothelial cells. ×280.


The actual stem cells for the corneal epithelium, called **corneolimbal**
**stem cells**, reside at the **corneoscleral limbus**, the junction of the cornea
and sclera. The microenvironment of this stem cell niche is important in
maintaining the stem cell population. It also acts as a barrier that prevents
migration of conjunctival epithelial cells to the corneal surface. The
**corneolimbal stem cells** may be partially or totally depleted by
disease or extensive injury, resulting in abnormalities of the corneal
surface that lead to **conjunctivalization** of the cornea, which is
characterized by vascularization, appearance of goblet cells, and an
irregular and unstable epithelium. These changes cause ocular
discomfort and reduced vision. Minor injuries of the corneal surface
heal rapidly by inducing stem cell proliferation and migration of cells
from the corneoscleral limbus to fill the defect.

Numerous free nerve endings in the corneal epithelium provide it with
extreme sensitivity to touch. Stimulation of these nerves (e.g., by small foreign
bodies) elicits blinking of the eyelids, flow of tears, and, sometimes, severe
pain. Microvilli present on the surface epithelial cells help retain the tear film
over the entire corneal surface. Drying of the corneal surface may cause
ulceration.


**DNA in the corneal epithelial cells is protected from UV light damage**
**by nuclear ferritin.**


Despite constant exposure of the corneal epithelium to ultraviolet (UV) light,
cancer of the corneal epithelium is extremely rare. Unlike the epidermis, which
is also exposed to UV light, melanin is not present as a defense mechanism in
the corneal epithelium. The presence of melanin in the cornea would diminish
light transmission. Instead, it has recently been shown that corneal epithelial
cell nuclei contain **ferritin**, an iron-storage protein. Experimental studies
with avian corneas have shown that **nuclear ferritin** protects the DNA
in the corneal epithelial cells from free radical damage caused by UV
light exposure.


**Bowman membrane is a homogeneous-appearing layer on which the**
**corneal epithelium rests.**


**Bowman membrane** (anterior basement membrane) is a homogeneous,
faintly fibrillar lamina that is approximately 8–10 μm thick. It lies between the


corneal epithelium and the underlying corneal stroma and ends abruptly at the
corneoscleral limbus. The collagen fibrils of Bowman membrane have a
diameter of about 18 nm and are randomly oriented. Bowman membrane
imparts some strength to the cornea, but more significantly, it acts as a
barrier to the spread of infections. It does not regenerate. Therefore, if
damaged, an opaque scar forms that may impair vision. In addition,
changes in Bowman membrane are associated with **recurrent corneal**
**erosions** .


**The corneal stroma constitutes 90% of the corneal thickness.**


The **corneal stroma**, also called **substantia propria**, is composed of about
60 thin lamellae. Each lamella consists of parallel bundles of collagen fibrils.
Located between the lamellae are nearly complete sheets of slender, flattened
fibroblasts. The collagen fibrils are very uniform, measuring approximately 23
nm in diameter and as long as 1 cm in length, and are arranged at
approximately right angles to those in adjacent lamellae (Fig. 24.5). The
ground substance of cornea contains **small leucine-rich proteoglycans**
**(SLRPs)**, which comprise sulfated glycosaminoglycans—chiefly, keratan
sulfate proteoglycan ( **lumican** ) and chondroitin sulfate proteoglycan
( **decorin** ). They are responsible for the 3D organization of collagen fibrils.
Lumican regulates the normal collagen fibril assembly in the cornea and is
critical to the development of a highly organized collagenous matrix.


**FIGURE 24.5.** **Electron micrograph of the corneal stroma.** This electron
micrograph shows parts of three lamellae and a portion of a corneal fibroblast
( _CF_ ) between two of the lamellae. Note that the collagen fibrils in adjacent
lamellae are oriented at right angles to one another. ×16,700.


**Corneal transparency is achieved by the regular arrangement of small**
**collagen fibrils and the spaces between them that are smaller than**
**one-half of a wavelength of visible light.**


The **transparency of the cornea** is directly related to the spaces between
collagen fibrils containing glycosaminoglycans and the size of the collagen
fibrils. If these spaces are smaller than one-half of a wavelength of visible
light, the cornea is clear and transparent. The uniform spacing of type I
collagen fibrils and lamellae, as well as the **orthogonal array** of the lamellae
(alternating layers at right angles), helps maintain corneal transparency.
Proteoglycans ( **lumican** ), along with **type V collagen**, regulate the precise
diameter and spacing of the type I collagen fibrils, maintaining corneal clarity.
The necessity for uniformity of collagen fibrils explains the ratio of type V to
type I collagen, which is much higher in the corneal stroma than in other


tissues. **Corneal swelling** after injury to the epithelium or endothelium
disrupts this precise array and leads to translucency or opacity of the
cornea. The hazy appearance of the cornea is related to the
enlargement of the spaces between collagen fibers. Lumican is
overexpressed during the wound healing process following corneal
injury. Normally, the cornea contains no blood vessels or pigments.
During an inflammatory response involving the cornea, large numbers
of neutrophils and lymphocytes migrate from the blood vessels of the
corneoscleral limbus and penetrate the stromal lamellae.


**Descemet membrane is an unusually thick basal lamina.**


**Descemet membrane** (posterior basement membrane) is the basal lamina of
corneal endothelial cells. It is intensely positive to periodic acid–Schiff (PAS)
and can be as thick as 10 μm. Descemet membrane has a felt-like appearance
and consists of an interwoven meshwork of fibers and pores. It separates the
corneal endothelium from the adjacent corneal stroma. Unlike Bowman
membrane, Descemet membrane readily regenerates after injury. It is
produced continuously but slowly thickens with age. Descemet
membrane also contributes to the diagnosis of **Wilson disease**, a rare
inherited disorder of copper metabolism that causes excessive
deposition of copper in organs and other tissues. A common
ophthalmologic finding in individuals with Wilson disease is the
presence of **Kayser–Fleischer rings** . These are caused by increased
depositions of copper within Descemet membrane. A Kayser–Fleischer
ring usually appears as a gold brown ring located in the periphery of
the cornea.

Descemet membrane extends peripherally beneath the sclera as a
trabecular meshwork forming the **pectinate ligament** . Strands from the
pectinate ligament penetrate the ciliary muscle and sclera and may help
maintain the normal curvature of the cornea by exerting tension on Descemet
membrane.


**The corneal endothelium provides for metabolic exchange between**
**the cornea and the aqueous humor.**


The **corneal endothelium** is a single layer of squamous cells covering the
surface of the cornea that faces the anterior chamber (Fig. 24.4c). The cells are
joined by well-developed zonulae adherentes, relatively leaky zonulae
occludentes, and desmosomes. Virtually, all of the metabolic exchanges of the
cornea occur across the endothelium. The endothelial cells contain many
mitochondria and vesicles and an extensive rough-surfaced endoplasmic
reticulum (rER) and Golgi apparatus. They demonstrate endocytotic activity
and are engaged in active transport. Na [+] /K [+] -activated ATPase is located on the
lateral plasma membrane.


Transparency of the cornea requires precise regulation of the water content
of the stroma. Physical or metabolic damage to the endothelium leads to
rapid **corneal swelling** and, if the damage is severe, corneal opacity.
Restoration of endothelial integrity is usually followed by deturgescence
(dehydration necessary to maintain the transparency), although
corneas can swell beyond their ability for self-repair. Such swelling can
result in permanent focal opacities caused by aggregation of collagen
fibrils in the swollen cornea. Essential sulfated glycosaminoglycans that
normally separate the corneal collagen fibers are extracted from the
swollen cornea.

Human **corneal endothelium** has a **limited proliferative capacity** .
Severely damaged endothelium can be repaired only by transplantation
of a donor cornea. Recent studies indicate that the periphery of the
cornea represents a regenerative zone of the corneal endothelial cells.
However, soon after **corneal transplantation**, endothelial cells exhibit
contact inhibition when exposed to the extracellular matrix of Descemet
membrane. The discovery that inhibitory factors released by Descemet
membrane prevent proliferation of endothelial cells has focused current
corneal research on the reversal or prevention of this inhibition with
exogenous growth factors.


**The sclera is an opaque layer that consists predominantly of dense**
**connective tissue.**


The **sclera** is a thick fibrous layer containing flat collagen bundles that pass in
various directions and in planes parallel to its surface. Both the collagen
bundles and the fibrils that form them are irregular in diameter and
arrangement. Interspersed between the collagen bundles are fine networks of
elastic fibers and a moderate amount of ground substance. Fibroblasts are
scattered among these fibers (Plate 24.4, page 1016).

The opacity of the sclera, like that of other dense connective tissues, is
primarily attributable to the irregularity of its structure. The sclera is pierced
by blood vessels, nerves, and the optic nerve (see Fig. 24.2). It is 1 mm thick
posteriorly, 0.3–0.4 mm thick at its equator, and 0.7 mm thick at the
corneoscleral margin or limbus.

The sclera is divided into three rather ill-defined layers:


The **episcleral layer (episclera)**, the external layer, is the loose connective
tissue adjacent to the periorbital fat.
The **substantia propria** ( **sclera proper**, also called **Tenon capsule** ) is
the investing fascia of the eye and is composed of a dense network of thick
collagen fibers.
The **suprachoroid lamina (lamina fusca)**, the inner aspect of the sclera,
is located adjacent to the choroid and contains thinner collagen fibers and


elastic fibers as well as fibroblasts, melanocytes, macrophages, and other
connective tissue cells.


In addition, the **episcleral space (Tenon space)** is located between the
episcleral layer and substantia propria of the sclera. This space and the
surrounding periorbital fat allow the eye to rotate freely within the orbit. The
tendons of the extraocular muscles attach to the substantia propria of the
sclera.


**The corneoscleral limbus is the transitional zone between the cornea**

**and the sclera that contains corneolimbal stem cells.**


At the **junction of the cornea and sclera** (Fig. 24.6 and Plate 24.4, page
1016), Bowman membrane ends abruptly. The overlying epithelium at this site
thickens from the 5 cell layers of the cornea to the 10–12 cell layers of the
conjunctiva. The surface of the limbus is composed of two distinct types of
epithelial cells: One type constitutes the conjunctival cells, and the other
constitutes the corneal epithelial cells. The basal layer of the limbus contains
the **corneolimbal stem cells** that generate and maintain the corneal
epithelium. These cells proliferate, differentiate, and migrate to the surface of
the limbus and then toward the center of the cornea to replace damaged
epithelial cells. As mentioned previously, this movement of cells at the
corneoscleral limbus also creates a barrier that prevents conjunctival
epithelium from migrating onto the cornea. At this junction, the corneal
lamellae become less regular as they merge with the oblique bundles of
collagen fibers of the sclera. An abrupt transition from the avascular cornea to
the well-vascularized sclera also occurs here.


**FIGURE 24.6.** **Schematic diagram of the structure of the eye.** This drawing
shows a horizontal section of the eyeball with color-coded layers of its wall.
**Upper inset.** Enlargement of the anterior and posterior chambers is shown in
more detail. Note the location of the iridocorneal angle and canal of Schlemm
(scleral venous sinus), which drains the aqueous humor from the anterior
chamber of the eye. **Lower inset.** Typical organization of the cells and nerve
fibers of the fovea.


The limbus region, specifically, the **iridocorneal angle**, contains the
apparatus for the outflow of aqueous humor (Fig. 24.7). In the stromal layer,
endothelium-lined channels called the **trabecular meshwork** (or **spaces of**
**Fontana** ) merge to form the **scleral venous sinus (canal of Schlemm)** .
This sinus encircles the eye (see Figs. 24.6 and 24.7). The aqueous humor is
produced by the ciliary processes that border the lens in the posterior chamber
of the eye. The fluid passes from the posterior chamber into the anterior
chamber through the valve-like potential opening between the iris and lens.
The fluid then passes through the openings in the trabecular meshwork in the
limbus region as it continues its course to enter the scleral venous sinus.
Collecting vessels in the sclera, called **aqueous veins** (of Ascher) because
they convey aqueous humor instead of blood, transport the aqueous humor to
episcleral and conjunctival (blood) veins located in the sclera. Changes in
the **iridocorneal angle** may lead to blockage in the drainage of
aqueous humor, causing **glaucoma** (see Folder 24.1, page 990). The


iridocorneal angle can be visualized during eye examination using a
**gonioscope**, a specialized optical device that uses mirrors or prisms to
reflect the light from the iridocorneal angle into the direction of the
observer. In conjunction with a slit lamp or operating microscope, the
ophthalmologist can examine this region to monitor various eye
conditions associated with glaucoma. The iridocorneal angle can be
also visualized using the **ultrasound biomicroscopy (UBM)** . This
high-resolution imaging technique utilizes a high-frequency ultrasound
transducer to visualize the narrowed iridocorneal angle in primary
angle-closure glaucoma.


**FIGURE 24.7.** **Photomicrograph of the ciliary body and iridocorneal angle.**
This photomicrograph of the human eye shows the anterior portion of the ciliary
body and parts of the _iris_ and _sclera_ . The inner surface of the ciliary body forms
radially arranged, ridge-shaped elevations, the _ciliary processes_, to which the
_zonular fibers_ are anchored. The ciliary body contains the _ciliary muscle_,
connective tissue with blood vessels of the vascular coat, and the ciliary
epithelium, which is responsible for the production of aqueous humor. Anterior
to the ciliary body, between the iris and the cornea, is the _iridocorneal angle_ .
The scleral venous sinus ( _canal of Schlemm_ ) is located in close proximity to
this angle and drains the aqueous humor to regulate intraocular pressure.
×120. The _inset_ shows that the ciliary epithelium consists of two layers, the
outer pigmented layer and the inner nonpigmented layer. ×480.


##### Glaucoma is a clinical condition resulting from increased intraocular

pressure over a sustained period of time. It can be caused by excessive
secretion of aqueous humor or impedance of the drainage of aqueous humor
from the anterior chamber. The internal tissues of the eye, particularly the
retina, are nourished by the diffusion of oxygen and nutrients from the
intraocular vessels. Blood flows normally through these vessels (including the
capillaries and veins) when the hydrostatic pressure within the vessels exceeds
the intraocular pressure. If the drainage of the aqueous humor is impeded, the
intraocular pressure increases because the layers of the eye do not allow the
wall to expand. This increased pressure interferes with normal retinal
nourishment and function, causing the retinal nerve fiber layer to atrophy (Fig.
F24.1.1).


**FIGURE F24.1.1.** **Glaucoma.** This image shows a view of the fundus of the left
eye in a patient with advanced glaucoma. As a result of the increased
intraocular pressure, retinal nerve fibers undergo atrophy and shrink in size.
Note a pale optic disc in the _center_ of the image with a less pronounced rim
due to atrophy of nerve fibers. Enlargement of the optic nerve cup (central area
of the optic disc) is also visible and a characteristic finding for glaucoma.


Compare this image to a normal retina in Figure 24.15. (Courtesy of Dr. Renzo
A. Zaldivar.) There are two major types of glaucoma:

##### Open-angle glaucoma is the most common type of glaucoma and the

leading cause of blindness among adults. The removal of aqueous humor is
obstructed because of reduced flow through the trabecular meshwork of the
iridocorneal angle into the scleral venous sinus (canal of Schlemm).
##### Angle-closure glaucoma (acute glaucoma) is less common and is

characterized by a narrowed iridocorneal angle that obstructs the inflow of
the aqueous humor into the scleral venous sinus. Usually, it is associated
with a sudden, painful, complete blockage of the scleral venous sinus and
can result in permanent blindness if not treated promptly.


Visual deficits associated with glaucoma include blurring of vision and
impaired dark adaptation (symptoms that indicate loss of normal retinal
function) and halos around lights (a symptom indicating corneal endothelial
damage). If the condition is not treated, the retina will be permanently
damaged, and blindness will occur. Treatment is directed toward lowering the
intraocular pressure by decreasing the rate of production of aqueous humor or
eliminating the cause of the obstruction of normal drainage. Topical
##### prostaglandin analogs (i.e., latanoprost, bimatoprost, travoprost) are the

first line of treatment for open-angle glaucoma. They are very effective in
reducing intraocular pressure by increasing the drainage of aqueous humor
##### into the canal of Schlemm. Carbonic anhydrase inhibitors, which were

used in the past to decrease the production of aqueous humor, have largely
been replaced by prostaglandin analogs that have fewer systemic side effects.

There are two main types of laser surgery to treat glaucoma. They facilitate
drainage of aqueous humor from the iridocorneal angle. Laser
##### trabeculoplasty utilizes a laser beam to induce focal scarring of the

trabecular meshwork. This results in mechanical stretching of the surrounding
untreated regions of the meshwork, which facilitates drainage of the aqueous
humor. Trabeculoplasty is often used in open-angle glaucoma when
##### medications are not effective or cause intolerable side effects. Iridotomy is

used in patients with angle-closure glaucoma. The laser beam incises a small
opening at the base of the iris, which widens the iridocorneal angle to allow
better drainage of aqueous humor.

### **Vascular Coat (Uvea)**


**The iris, the most anterior part of the vascular coat, forms a**
**contractile diaphragm in front of the lens.**


The **iris** arises from the anterior border of the ciliary body (see Fig. 24.7) and
is attached to the sclera about 2 mm posterior to the corneoscleral junction.
The **pupil** is the central aperture of this thin disc. The iris is pushed slightly
forward as it changes in size in response to light intensity. It consists of a
highly vascularized connective tissue stroma that is covered on its posterior
surface by highly pigmented cells, the **posterior pigment epithelium** (Fig.
24.8). The basal lamina of these cells faces the posterior chamber of the eye.
The degree of pigmentation is so great that neither the nucleus nor the
character of the cytoplasm can be seen in the light microscope. Located
beneath this layer is a layer of myoepithelial cells, the **anterior pigment**
**myoepithelium** . The apical (posterior) portions of these myoepithelial cells
are laden with melanin granules, which effectively obscure their boundaries
with the adjacent posterior pigment epithelial cells. The basal (anterior)
portions of myoepithelial cells possess processes containing contractile
elements that extend radially and collectively make up the **dilator pupillae**
**muscle** of the iris. The contractile processes are enclosed by a basal lamina
that separates them from the adjacent stroma.


**FIGURE 24.8.** **Structure of the iris. a.** This schematic diagram shows the
layers of the iris. Note that the pigmented epithelial cells are reflected as occurs
at the pupillary margin of the iris. The two layers of pigmented epithelial cells
are in contact with the dilator pupillae muscle. The incomplete layer of
fibroblasts and stromal melanocytes is indicated on the anterior surface of the
iris. **b.** Photomicrograph of the iris showing the histologic features of this
structure. The _lens_, which lies posterior to the iris, is included for orientation.
The iris is composed of a _connective tissue_ stroma covered on its posterior


surface by the posterior pigment epithelium. The basal lamina (not visible)
faces the posterior chamber of the eye. Because of intense pigmentation, the
histologic features of these cells are not discernible. Just anterior to these cells
is the anterior pigment myoepithelium layer (the _dashed line_ separates the two
layers). Note that the posterior portion of the myoepithelial cells contains
melanin, whereas the anterior portion contains contractile elements forming the
dilator pupillae muscle of the iris. The sphincter pupillae muscle is evident in
the stroma. The color of the iris depends on the number of _stromal melanocytes_
scattered throughout the connective tissue stroma. At the _bottom_, note the
presence of the lens. ×570.


Constriction of the pupil is produced by smooth muscle cells located in the
stroma of the iris near the pupillary margin of the iris. These circumferentially
oriented cells collectively compose the **sphincter pupillae muscle** .

The anterior surface of the iris reveals numerous ridges and grooves that
can be seen in clinical examination with the ophthalmoscope. When this
surface is examined in the light microscope, it appears as a discontinuous layer
of fibroblasts and melanocytes. The number of melanocytes in the stroma is
responsible for variation in eye color. The function of these **pigment-**
**containing cells** in the iris is to absorb light rays. If there are few
melanocytes in the stroma, the color of the iris is derived from light
reflected from the pigment present in the cells of the iris’s posterior
surface, giving it a blue appearance. With increasing amounts of
pigment present in the stroma, the iris color changes from blue to
shades of greenish blue, gray, and, finally, brown.


**The sphincter pupillae is innervated by parasympathetic nerves; the**
**dilator pupillae muscle is under sympathetic nerve control.**


The **size of the pupil** is controlled by contraction of the sphincter pupillae
and dilator pupillae muscles. The process of **adaptation** (increasing or
decreasing the size of the pupil) ensures that only the appropriate amount of
light enters the eye. Two muscles are actively involved in adaptation:


The **sphincter pupillae muscle**, a circular band of smooth muscle cells
(Plate 24.3, page 1014), is innervated by parasympathetic nerves carried in
the oculomotor nerve (cranial nerve III) and is responsible for reducing
pupillary size in response to bright light. Failure of the pupil to respond
when light is shined into the eye—“ **pupil fixed and dilated** ”—is an
important clinical sign showing a lack of nerve or brain function.
The **dilator pupillae muscle** is a thin sheet of radially oriented contractile
processes of pigmented myoepithelial cells constituting the anterior pigment
epithelium of the iris. This muscle is innervated by sympathetic nerves from
the superior cervical ganglion and is responsible for increasing pupillary
size in response to dim light.


Just before **ophthalmoscopic examination**, mydriatic agents such
as **atropine** are given as eye drops to cause dilation of the pupil.
Acetylcholine (ACh) is the neurotransmitter of the parasympathetic
nervous system (it innervates the sphincter pupillae muscle); the
addition of atropine blocks muscarinic acetylcholine receptors,
temporally blocking the action of the sphincter muscle, and leaving the
**pupil** **wide** **open** and unreactive to light originating from
ophthalmoscope.


**The ciliary body is the thickened anterior portion of the vascular coat**
**and is located between the iris and the choroid.**


The **ciliary body** extends about 6 mm from the root of the iris posterolaterally
to the **ora serrata** (see Fig. 24.2). As seen from behind, the lateral edge of the
ora serrata bears 17–34 grooves or crenulations. These grooves mark the
anterior limit of both the retina and the choroid. The anterior third of the
ciliary body has approximately 75 radial ridges or **ciliary processes** (see Fig.
24.7). The fibers of the zonule arise from the grooves between the ciliary

processes.

The layers of the ciliary body are similar to those of the iris and consist of
a stroma and an epithelium. The stroma is divided into two layers:


An **outer layer** of smooth muscle, the **ciliary muscle**, makes up the bulk
of the ciliary body.
An **inner vascular region** extends into the ciliary processes.


The epithelial layer covering the internal surface of the ciliary body is a
direct continuation of the two layers of the retinal epithelium (see Fig. 24.1).


**The ciliary muscle is organized into three functional portions or**
**groups of smooth muscle fibers.**


The smooth muscle of the ciliary body has its origin in the scleral spur, a
ridge-like projection on the inner surface of the sclera at the corneoscleral
junction. The muscle fibers spread out in several directions and are classified
into three functional groups on the basis of their direction and insertion:


The **meridional (or longitudinal) portion** consists of the outer muscle
fibers that pass posteriorly into the stroma of the choroid. These fibers
function chiefly in stretching the choroid. It also may help open the
iridocorneal angle and facilitate drainage of the aqueous humor.
The **radial (or oblique) portion** consists of deeper muscle fiber bundles
that radiate in a fan-like manner to insert into the ciliary body. Its
contraction causes the lens to flatten and thus focus on distant vision.


The **circular (or sphincteric) portion** consists of inner muscle fiber
bundles oriented in a circular pattern that forms a sphincter. It reduces the
tension on the lens, causing the lens to accommodate for near vision.


Examination of a histologic preparation does not clearly reveal the
arrangement of the muscle fibers. Rather, the organizational grouping is based
on microdissection techniques.


**Ciliary processes are ridge-like extensions of the ciliary body from**
**which zonular fibers emerge and extend to the lens.**


**Ciliary processes** are thickenings of the inner vascular region of the ciliary
body. They are continuous with the vascular layers of the choroid. Scattered
macrophages containing melanin pigment granules and elastic fibers are
present in these processes (Plate 24.3, page 1014). The processes and the
ciliary body are covered by a double layer of columnar epithelial cells, the
**ciliary epithelium**, which was originally derived from the two layers of the
optic cup. The ciliary epithelium has three principal functions:


Secretion of **aqueous humor**
Participation in the **blood–aqueous barrier** (part of the **blood–ocular**
**barrier** )
Secretion and anchoring of the **zonular fibers** that form the **suspensory**
**ligament of the lens**


The inner cell layer of the ciliary epithelium has a basal lamina facing the
posterior and vitreous chambers. The cells in this layer are nonpigmented. The
cell layer that has its basal lamina facing the connective tissue stroma of the
ciliary body is heavily pigmented and is directly continuous with the
pigmented epithelial layer of the retina. The **double-layered ciliary**
**epithelium** continues over the iris, where it becomes the posterior pigmented
epithelium and anterior pigmented myoepithelium. The zonular fibers extend
from the basal lamina of the nonpigmented epithelial cells of the ciliary
processes and insert into the lens capsule (the thickened basal lamina of the
lens).


**The blood–aqueous barrier separates the interior environment of the**
**eye from the blood entering the ciliary body.**


The **cells of the nonpigmented layer** have all the characteristics of a fluidtransporting epithelium, including complex cell-to-cell junctions with a welldeveloped zonula occludens, extensive lateral and basal plications, and
localization of Na [+] /K [+] -ATPase in the lateral plasma membrane. In addition,
they have an elaborate rER and Golgi complex, consistent with their role in the
secretion of zonular fibers. Tight junctions (zonulae occludentes) between the


nonpigmented ciliary epithelial cells are responsible for maintaining the
**blood–aqueous barrier** . This barrier restricts free diffusion across the ciliary
epithelium to maintain the unique environment of the aqueous humor, which is
quite different from that of blood vessels and stroma of the ciliary body. The
blood–aqueous barrier contributes to the nutrition and function of the cornea
and the lens. **Disruption of the blood–aqueous barrier** may be
observed in ocular inflammation, intraocular surgery, trauma, or
vascular diseases. The aqueous humor becomes cloudy because of
the leakage of plasma proteins (fibrinogen) and migration of
inflammatory cells from the stroma of the ciliary body and iris into the
posterior and anterior chambers of the eye.

The **cells of the pigmented layer** have a less developed junctional zone
and often exhibit large, irregular lateral intercellular spaces. Both desmosomes
and gap junctions hold together the apical surfaces of the two cell layers,
creating discontinuous “luminal” spaces called **ciliary channels** .


**The aqueous humor is derived from plasma and maintains intraocular**

**pressure.**


The **aqueous humor** is secreted by the double-layered ciliary epithelium and
originates from blood capillaries. It is similar in ionic composition to plasma
but contains less than 0.1% protein (compared to 7% protein in plasma). The
main functions of the aqueous humor are to maintain **intraocular pressure**
and to provide nutrients and remove metabolites from the avascular tissues of
the cornea and lens. The aqueous humor passes from the ciliary body toward
the lens and then between the iris and the lens, before it reaches the anterior
chamber of the eye (see Fig. 24.6). In the anterior chamber of the eye, the
aqueous humor passes laterally to the angle formed between the cornea and the
iris. Here, it penetrates the tissues of the limbus as it enters the labyrinthine
spaces of the limbus’s trabecular meshwork in the iridocorneal angle and
finally reaches the **canal of Schlemm**, which communicates with the veins of
the sclera (see Folder 24.1). Normal turnover of the aqueous humor in the
human eye is approximately once every 1.5–2 hours.


**The choroid is the portion of the vascular coat that lies deep into the**
**retina.**


The **choroid** is a dark brown vascular sheet only 0.25 mm thick posteriorly
and 0.1 mm thick anteriorly. It lies between the sclera and the retina (see Fig.
24.1).

Two layers can be identified in the choroid:


**Choriocapillary layer**, an inner vascular layer
**Bruch membrane**, a thin, amorphous hyaline membrane


The choroid is attached firmly to the sclera at the margin of the optic nerve.
A potential space, the **perichoroidal space** (between the sclera and the
retina), is traversed by thin, ribbon-like branching lamellae or strands that pass
from the sclera to the choroid. These lamellae originate from the
**suprachoroid lamina** (lamina fusca) and consist of large, flat melanocytes
scattered between connective tissue elements, including collagen and elastic
fibers, fibroblasts, macrophages, lymphocytes, plasma cells, and mast cells.
The lamellae pass inward to surround the vessels in the remainder of the
choroid layer. Free smooth muscle cells, not associated with blood vessels, are
present in this tissue. Lymphatic channels called **epichoroid lymph spaces**,
long and short posterior ciliary vessels, and nerves on their way to the front of
the eye are also present in the suprachoroid lamina.

Most of the blood vessels decrease in size as they approach the retina. The
largest vessels continue forward beyond the ora serrata into the ciliary body.
These vessels can be seen with an ophthalmoscope. The large vessels are
mostly veins that course in whorls before passing obliquely through the sclera
as vortex veins. The inner layer of vessels, arranged in a single plane, is called
the **choriocapillary layer** . The vessels of this layer provide nutrients to the
cells of the retina. The fenestrated capillaries have lumina that are large and
irregular in shape. In the region of the fovea, the choriocapillary layer is
thicker, and the capillary network is denser. This layer ends at the ora serrata.

**Bruch membrane**, also called the **lamina vitrea**, measures 1–4 μm in
thickness and lies between the choriocapillary layer and the pigment
epithelium of the retina. It runs from the optic nerve to the ora serrata, where it
undergoes modifications before continuing into the ciliary body. Bruch
membrane is a thin, amorphous refractile layer. The transmission electron
microscope (TEM) reveals that it consists of a multilaminar sheet containing a
center layer of elastic and collagen fibers. Five different layers are identified in
Bruch membrane:


The basal lamina of the endothelial cells of the choriocapillary layer
A layer of collagen fibers approximately 0.5 μm thick
A layer of elastic fibers approximately 2 μm thick
A second layer of collagen fibers (thus forming a “sandwich” around the
intervening elastic tissue layer)
The basal lamina of the RPE cells


At the ora serrata, the collagenous and elastic layers disappear into the
ciliary stroma, and Bruch membrane becomes continuous with the basal
lamina of the RPE of the ciliary body.

### **Retina**


**The retina represents the innermost layer of the eye.**


The **retina**, derived from the inner and outer layers of the optic cup, is the
innermost of the three concentric layers of the eye (see Fig. 24.1). It consists of
two basic layers:


The **neural retina** or **retina proper** is the inner layer that contains the
photoreceptor cells.
The **retinal pigment epithelium (RPE)** is the outer layer that rests on and
is firmly attached through the Bruch membrane to the choriocapillary layer
of the choroid.


A potential space exists between the two layers of the retina. The two
layers may be separated mechanically in the preparation of histologic
specimens. Separation of the layers, “ **retinal detachment** ” (see Folder
24.2), also occurs in the living state because of eye disease or trauma.


A potential space exists in the retina as a vestige of the space between the
apical surfaces of the two epithelial layers of the optic cup. If this space
expands, the neural retina separates from the retinal pigment epithelium
(RPE), which remains attached to the choroid layer. This condition is called
**retinal detachment** . As a result of retinal detachment, the photoreceptor
cells are no longer supplied by nutrients from the underlying vessels in the
choriocapillary plexus of the choroid.

Clinical symptoms of retinal detachment include visual sensations
commonly described as a “shower of pepper” or floaters. These are
caused by red blood cells extravasated from the capillary vessels that have
been injured during the retinal tear or detachment. In addition, some
individuals describe sudden flashes of light as well as a “web” or “veil” in
front of the eye in conjunction with the onset of floaters. A detached retina
can be observed and diagnosed during ophthalmoscopic eye examination
(Fig. F24.2.1).


**FIGURE F24.2.1.** **Retinal detachment.** This image shows a view of the fundus of
the right eye in a patient with retinal detachment. The central retinal vessels
emerging from the optic disc are in focus, but in the _area of the retinal detachment,_
they appear to be out of focus. Because the area of retinal detachment is elevated
(note multiple ridges and shadows), it is located anterior to the plane of focus of the
ophthalmoscope. (Courtesy of Dr. Renzo A. Zaldivar.) Another common retinal
condition occurs with aging. As the vitreous body ages (in the sixth and seventh
decades of life), it tends to shrink and pull away from the neural retina, which
causes single or multiple tears in the neural retina.


If not repositioned quickly, the detached area of the retina will undergo
necrosis, resulting in blindness. An argon laser is often used to repair
retinal detachment by photocoagulating the edges of the detachment and
producing scar tissue. This method prevents the retina from further
detachment and facilitates the repositioning of photoreceptor cells.


In the neural retina, two regions or portions that differ in function are
recognized:


The **nonphotosensitive region** (nonvisual part), located anterior to the
ora serrata, lines the inner aspect of the ciliary body and the posterior
surface of the iris (this portion of the retina is described in the sections on
the iris and ciliary body).


The **photosensitive region** (optic part) lines the inner surface of the eye
posterior to the ora serrata, except where it is pierced by the optic nerve (see
Fig. 24.1).


The site where the optic nerve joins the retina is called the **optic disc** or
**optic papilla** . Because the optic disc is devoid of photoreceptor cells, it is a
blind spot in the visual field. The **fovea centralis** is a shallow depression
located about 2.5 mm lateral to the optic disc. It is the area of greatest visual
acuity. The visual axis of the eye passes through the fovea. A yellowpigmented zone called the **macula lutea** surrounds the fovea. In relative
terms, the fovea is the region of the retina that contains the highest
concentration and most precisely ordered arrangement of visual elements. The
region of the retina surrounding the macula lutea may be affected in
older individuals by **age-related macular degeneration** (see Folder
24.3).


**Age-related macular degeneration (ARMD)** is the most common
cause of blindness in older individuals. Although the cause of this disease
is still unknown, evidence suggests both genetic and environmental
(ultraviolet [UV] irradiation, drugs) components. The disease causes loss
of central vision, although peripheral vision remains unaffected. Two forms
of ARMD are recognized: a dry (atrophic, nonexudative) form and a wet
(exudative, neovascular) form. The latter is considered a complication of
the first. **Dry ARMD** is the most common form (90% of all cases) and
involves degenerative lesions localized in the area of the macula lutea.
The degenerative lesions include **drusen**, which are focal thickenings of
Bruch membrane, atrophy, depigmentation of the RPE, and obliteration of
capillaries in the underlying choroid layer. These changes lead to the
deterioration of the overlying photosensitive retina, resulting in the
formation of blind spots in the visual field (Fig. F24.3.1). **Wet ARMD** is a
complication of dry ARMD caused by neovascularization of blind spots of
the retina in the large drusen. These newly formed, thin, fragile vessels
frequently leak and produce exudates and hemorrhages in the space just
beneath the retina, resulting in fibrosis and scarring. These changes are
responsible for the progressive loss of central vision over a short time. The
treatment of wet ARMD includes conventional **laser photocoagulation**
therapy and pharmacologic therapy with intravitreal injection of
ranibizumab, a **vascular endothelial growth factor (VEGF) inhibitor** .
Other surgical methods, such as **macular translocation**, have been
recently introduced. In this procedure, the retina is detached, translocated,
and reattached in a new location, away from the choroid neovascular


tissue. Conventional laser treatment is then applied to destroy pathologic
vessels without destroying central vision.


**FIGURE F24.3.1.** **Photograph depicting the visual field in individuals with age-**
**related macular degeneration.** Note that central vision is absent because of the
changes in the macula region of the retina. To maximize their remaining vision,
individuals with this condition are instructed to use eccentric fixation of their eyes.

##### **Layers of the retina**


**Ten layers of cells and their processes constitute the retina.**


Before discussing the **ten layers of the retina**, it is important to identify the
types of cells found there. This identification will aid in understanding the
functional relationships of the cells. Studies of the retina in primates have
identified at least 15 types of neurons that form at least 38 different types of
synapses. For convenience, neurons and supporting cells can be classified into


four groups of cells (Fig. 24.9):


**FIGURE 24.9.** **Schematic drawing and photomicrograph of the layers of**
**the retina.** On the basis of histologic features that are evident in the
photomicrograph _on right_, the retina can be divided into 10 layers. The layers
correspond to the diagram _on left_, which shows the distribution of major cells of
the retina. Note that light enters the retina and passes through its inner layers
before reaching the photoreceptors of the rods and cones that are closely
associated with the retinal pigment epithelium. Also, the interrelationship
between the bipolar neurons and ganglion cells that carry electrical impulses
from the retina to the brain is clearly visible. Bruch membrane (lamina vitrea)
separates the inner layer of the vascular coat (choroid) from the retinal pigment
epithelium. ×440.


**Photoreceptor cells** —the retinal rods and cones
**Conducting neurons** —bipolar neurons and ganglion cells
**Association neurons** and others—horizontal, centrifugal, interplexiform,
and amacrine neurons
**Supporting (neuroglial) cells** —Müller cells, microglial cells, and
astrocytes


The specific arrangement and associations of the nuclei and processes of
these cells form 10 retinal layers that can be seen with the light microscope.
The layers of the retina can also be imaged and examined in living
individuals using spectral-domain optical coherence tomography (see


Folder 24.4). The 10 layers of the retina, from outside inward, are as follows
(see Fig. 24.9): FOLDER 24.4

##### **CLINICAL CORRELATION: CLINICAL IMAGING OF THE** **RETINA**


The standard ophthalmoscopic examination of the eye has been recently
##### supplemented by a new examination technique that utilizes spectral- domain optical coherence tomography (SD OCT). This noninvasive

and noncontact examination is not only useful in visualizing the retinal
surface, but it also provides a high-resolution cross-sectional image of the
retina in vivo. All histologic layers of the retina can be easily differentiated
with SD OCT (Fig. F24.4.1), and they can be objectively measured for tissue
thickness and change. SD OCT technology is based on comparisons of spectral
characteristics of the reflected light beam from the retina with those of the
reference beam. For this purpose, an infrared laser beam (~840 nm wavelength
with 50 nm bandwidth) is used that is able to produce images at 5-μm
resolution. The laser beam passes through the structures of the eye and is
partially absorbed and partially reflected depending on tissue characteristics.
The reflected light is detected by a multichannel spectrometer, and the
interference pattern is compared to the reference beam using complex
computer algorithms. The spectral differences are used to construct the crosssectional (line) scans as shown in Figure F24.4.1 or the three-dimensional
images of the retina as shown in Figure F24.4.2. Introduced in the 1990s, the
SD OCT has revolutionized the management and diagnosis of many eye
diseases. SD OCT established itself as an imaging modality of choice in
##### glaucoma (measurement of optic nerve and retinal nerve fiber layer) and retinal diseases. It is used for the early and accurate detection of macular degeneration, retinal detachment, macular holes, epiretinal membranes, and optic disc pits and for the detection of fluid accumulation within the retina that occurs in conditions such as diabetic retinopathy, cystoid macular edema, and central serous choroidopathy .


**FIGURE F24.4.1.** **Spectral-domain optical coherence tomography (SD**
**OCT) cross-sectional (line) image of the retina in a healthy eye.** The _upper_
image represents a normal cross-sectional image of the retina containing fovea
and optic disc on the _right_ side of the image. The optically transparent vitreous
body is invisible and appears as the _black_ region in the upper part of the image.
Hyperreflective and hyporeflective bands of retinal tissue correspond to the
histologic layers of the retina. Note the photoreceptor layer containing rods and
cones as well the retinal pigment epithelium are well defined and are separated
from the choroid layer containing blood vessels. (Courtesy of Drs. Andrew J.


Barkmeier and Denise M. Lewison.)


**FIGURE F24.4.2.** **Spectral-domain optical coherence tomography (SD**
**OCT) three-dimensional image of the retina of a healthy right eye.** The
scan area is ~12 mm × 9 mm in size and includes a portion of the optic disc ( _on_
_the left_ ) and fovea ( _on the right_ ). A three-dimensional data set is acquired from
four scans (two vertical and two horizontal), which is then processed with a
motion-correction technology (MCT) algorithm. The MCT algorithm analyzes
and compares the vascular pattern in each of the scans and reduces artifacts
and image distortions associated with eye movement. This image has two
parts. The upper false-color image (optical densities are coded in different
colors) shows the surface and thickness of all layers of the retina and
represents a motion-corrected, three-dimensional volume rendering of the
entire data set. The lower grayscale vascular map image (optical densities are
coded in grayscale) is a two-dimensional image created by summing all the
pixels in each column. It is curved to match the curvature of the eye. The letters
S (for superior) and T (for temporal) on the eye orientation icon in the _lower_
_right corner_ provide reference to the positioning of the scan in the patient’s eye.
(Image courtesy of Dr. Pravin Dugel, Phoenix, Arizona.)


**1.** **Retinal pigment epithelium (RPE)** —the outer layer of the retina,

actually not part of the neural retina but intimately associated with it


**2.** **Layer of rods and cones** —contains the outer and inner segments of

photoreceptor cells
**3.** **Outer limiting membrane** —the apical boundary of Müller cells
**4.** **Outer nuclear layer** —contains the cell bodies (nuclei) of retinal rods and


cones
**5.** **Outer plexiform layer** —contains the processes of retinal rods and cones

and processes of the horizontal, amacrine, and bipolar cells that connect to
them

**6.** **Inner nuclear layer** —contains the cell bodies (nuclei) of horizontal,

amacrine, bipolar, and Müller cells
**7.** **Inner plexiform layer** —contains the processes of horizontal, amacrine,

bipolar, and ganglion cells that connect to each other
**8.** **Ganglion cell layer** —contains the cell bodies (nuclei) of ganglion cells
**9.** **Layer of optic nerve fibers** —contains processes of ganglion cells that

lead from the retina to the brain
**10.** **Inner limiting membrane** —composed of the basal lamina of Müller cells


Each of the layers is more fully described in the following sections (see
corresponding numbers).


**The cells of the retinal pigment epithelium (layer 1) have extensions**
**that surround the processes of the rods and cones.**


The **RPE** is a single layer of cuboidal cells about 14 μm wide and 10–14 μm
tall. The cells rest on Bruch membrane of the choroid layer. The pigment cells
are tallest in the fovea and adjacent regions, which account for the darker color
of this region.

Adjacent RPE cells are connected by a junctional complex consisting of
gap junctions and elaborate zonulae occludentes and adherentes. This
junctional complex is the site of the **blood–retina barrier** . This barrier makes
the retinal vessels impermeable to molecules larger than 20–30 kDa.

The pigment cells have cylindrical sheaths on their apical surface that are
associated with, but do not directly contact, the tip of the photoreceptor
processes of the adjacent rod and cone cells. Complex cytoplasmic processes
project for a short distance between the photoreceptor cells of the rods and
cones. Numerous elongated melanin granules, unlike those found elsewhere in
the eye, are present in many of these processes. They aggregate on the side of
the cell nearest the rods and cones and are the most prominent feature of the
cells. The nucleus with its many convoluted infoldings is located near the
basal plasma membrane adjacent to Bruch membrane.

The cells also contain material phagocytosed from the processes of the
photoreceptor cells in the form of lamellar debris (lipofuscin) contained in
residual bodies or phagosomes. These lipofuscin granules reside in the basal
cytoplasm of the RPE cell and are relatively difficult to detect in routine


hematoxylin and eosin (H&E) preparation. Because the lipofuscin pigment is
fluorescent, it can be clearly seen in the UV fluorescent microscope. A
supranuclear Golgi apparatus and an extensive network of smooth-surfaced
endoplasmic reticulum (sER) surround the melanin granules and residual
bodies that are present in the cytoplasm.

The **RPE** serves several important functions, including the following:


It **absorbs light** passing through the neural retina to **prevent reflection**
and resultant glare.
It isolates the retinal cells from blood-borne substances. It serves as a major
component of the **blood–retina barrier** via tight junctions between RPE
cells.
It participates in **restoring photosensitivity** to visual pigments that were
dissociated in response to light. The metabolic apparatus for visual pigment
resynthesis is present in the RPE cells.
It **phagocytoses and disposes of membranous discs** from the rods
and cones of the retinal photoreceptor cells.


**The rods and cones of the photoreceptor cell (layer 2) extend from the**
**outer layer of the neural retina to the pigment epithelium.**


The **rods** and **cones** are the outer segments of photoreceptor cells whose
nuclei form the outer nuclear layer of the retina (Figs. 24.9 and 24.10). The
light that reaches the photoreceptor cells must first pass through all of the
internal layers of the neural retina. The rods and cones are arranged in a
palisade manner; therefore, in the light microscope, they appear as vertical
striations.


**FIGURE 24.10.** **Schematic diagram of the ultrastructure of rod and cone**
**cells.** The outer segments of the rods and cones are closely associated with
the adjacent pigment epithelium.


The retina contains approximately **120 million rods** and **7 million**
**cones** . They are not distributed equally throughout the photosensitive part of
the retina. The **highest density of cones** is detected in the **fovea centralis**,
which corresponds to the highest visual acuity and best color vision (Fig.
24.11). The highest density of rods is outside the fovea centralis, and their
density steadily decreases toward the periphery of the retina. Rods are not
present in the fovea centralis nor at the optic disc, which is devoid of any
photoreceptors (see Fig. 24.11). The rods are about 2 μm thick and 50 μm long
(ranging from about 60 μm at the fovea to 40 μm peripherally). The cones vary
in length from 85 μm at the fovea to 25 μm at the periphery of the retina.


**FIGURE 24.11.** **Distribution of rods and cones in the human eye.** This
graph shows the density of rods and cones per mm [2] across the retina. The
peak number of cones occurs in the fovea centralis, where it reaches ~150,000


cones/mm [2] . Rod density peaks about 20 degrees from the visual axis and is
roughly the same as that of cones. Rods density decreases toward the
periphery of the retina. Note that there are no photoreceptors at the optic disc.


**Rods are sensitive in low light and produce black-and-white images;**
**cones are less sensitive in low light and produce color images.**


Functionally, the **rods** are more **sensitive to light** and are the receptors used
during periods of low light intensity (e.g., at dusk or at night). The rod
pigments have a maximum absorption at 496 nm of visual spectrum, and the
image provided is one composed of gray tones (a “black-and-white picture”).
In contrast, the **cones** exist in **three classes** : **L, M, and S** (long-, middle-,
and short-wavelength sensitive, respectively) that cannot be distinguished
morphologically. They are less sensitive to low light but more sensitive to red,
green, and blue regions of the visual spectrum. Each class of cones contains a
different visual pigment molecule that is activated by the absorption of light at
the **blue** (420 nm), **green** (531 nm), and **red** (588 nm) ranges in the color
spectrum. Cones provide a visual image composed of color by mixing the
appropriate proportion of red, green, and blue light. For a description of
different types of color blindness, see Folder 24.5.


In individuals with normal color vision, the three primary colors (red, green,
and blue) are combined to achieve the full spectrum of color vision. These
individuals are called **trichromats** and possess three independent
channels for conveying color information that are derived from three
different classes of cones (L—red sensitive; M—green sensitive; and S—
blue sensitive). Approximately 90% of trichromats can apperceive any
given color from impulses generated in all three classes of cones. Some
individuals have an impairment of normal color vision, which occurs when
one of the cones is altered in its spectral sensitivity. For example, about
6% of trichromats matches colors with an unusual proportion of red and
green. These individuals are called **anomalous trichromats** .

**Color blindness** is a condition in which individuals are missing or
have a defect in a specific class of cones. True color-blind individuals are
**dichromats** and have a defect either in the L, M, or S cones. In this
condition, the affected cones are completely missing. Dichromats can only
distinguish different colors by matching the impulses generated by the two
remaining normal classes of cones.

Three major types of color blindness have been identified:


**Protanopia** is characterized as a defect affecting the long-wavelength
L cones responsible for red vision. The genes encoding L cone
photoreceptor proteins are located on the X chromosome; therefore,


protanopia is a sex-linked disorder affecting mainly males (1% of the
male population). These individuals have difficulty distinguishing
between blue and green as well as red and green colors; thus, this color
vision deficiency is a serious risk factor in driving (Fig. F24.5.1).


**FIGURE F24.5.1.** **Color blindness.** This chart shows the six-color spectrum in
normal color vision and in individuals with the three types of color blindness.


**Deuteranopia** is characterized as a defect affecting the middlewavelength M cones responsible for green vision. Deuteranopia is the
most common form of color blindness, affecting about 5% of the male
population. It is also a sex-linked disorder because the genes encoding
M cone photoreceptor proteins are located in the same region of the X
chromosome as the genes for L cones. Similar to protanopia, red and
green are the main problem colors (see Fig. F24.5.1).
**Tritanopia** is characterized as a defect affecting the short-wavelength
S cones responsible for blue vision (see Fig. F24.5.1). The defect is
autosomal and involves mutation of a single gene encoding S cone
photoreceptor proteins that reside on chromosome 7. This color
blindness occurs very rarely (1 in 10,000) and affects women and men
equally.


Each rod and cone photoreceptor consists of three parts:


The **outer segment** of the photoreceptor is roughly cylindrical or conical
(hence, the descriptive name **rod** or **cone** ). This portion of the
photoreceptor is intimately related to microvilli projecting from the adjacent
pigment epithelial cells.
The **connecting stalk** contains a cilium composed of nine peripheral
microtubule doublets extending from a basal body. The connecting stalk
appears as the constricted region of the cell that joins the inner to the outer
segment. In this region, a thin, tapering process called the **calyceal**
**process** extends from the distal end of the inner segment to surround the
proximal portion of the outer segment (see Fig. 24.10).
The **inner segment** is divided into an outer **ellipsoid** and an inner **myoid**
**portion** . This segment contains a typical complement of organelles
associated with a cell that actively synthesizes proteins. A prominent Golgi
apparatus, rER, and free ribosomes are concentrated in the myoid region.
Mitochondria are most numerous in the ellipsoid region. Microtubules are
distributed throughout the inner segment. In the outer ellipsoid portion,
cross-striated fibrous rootlets may extend from the basal body among the
mitochondria.


The outer segment is the site of photosensitivity, and the inner segment
contains the metabolic machinery that supports the activity of the
photoreceptor cells. The outer segment is considered a highly modified cilium
because it is joined to the inner segment by a short connecting stalk containing
a basal body (Fig. 24.12a).


**FIGURE 24.12.** **Electron micrographs of portions of the inner and outer**
**segments of cones and rods. a.** This electron micrograph shows the junction
between the inner and outer segments of the rod cell. The outer segments
contain the horizontally flattened discs. The plane of this section passes
through the connecting stalk and cilium. A centriole, a cilium and its basal body,
and a calyceal process are identified. ×32,000. **b.** Another electron micrograph
shows a similar section of a cone cell. The interior of the discs in the outer
segment of the cone is continuous with the extracellular space ( _arrows_ ).
×32,000. (Courtesy of Dr. Toichiro Kuwabara.) With the TEM, 600–1,000
regularly spaced horizontal **membranous discs** are seen in the outer segment
(Fig. 24.12). In rods, these discs are membrane-bound structures measuring
about 2 μm in diameter. They are enclosed within the plasma membrane of the
outer segment (see Fig. 24.12a). The parallel membranes of the discs are
about 6 nm thick and are continuous at their ends. The central enclosed space
is about 8 nm across. In both rods and cones, the membranous discs are


formed from repetitive transverse infolding of the plasma membrane in the
region of the outer segment near the cilium. Autoradiographic studies have
demonstrated that rods form new discs by infolding of the plasma membrane
throughout their life span. Discs are formed in cones in a similar manner but
are not replaced on a regular basis.


Rod discs lose their continuity with the plasma membrane from which they
are derived soon after they are formed. They then pass like a stack of plates,
proximally to distally, along the length of the cylindrical portion of the outer
segment until they are eventually shed and phagocytosed by the pigment
epithelial cells. Thus, each rod disc is a membrane-enclosed compartment
within the cytoplasm. Discs within the cones retain their continuity with the
plasma membrane (Fig. 24.12b).


**Rod cells contain the visual pigment rhodopsin; cone cells contain**
**the visual pigment iodopsin.**


**Rhodopsin** (also called **visual purple** ) is a 39-kDa protein in rod cells that
initiates the visual stimulus when it is bleached by light. Rhodopsin is present
in globular form on the outer surface of the lipid bilayer (on the cytoplasmic
side) of the membranous discs. In the cone cells, the visual pigment protein on
the membranous discs is the photopigment **iodopsin** . Each cone cell is
specialized to respond maximally to one of three colors: red, green, or blue.
Both rhodopsin and iodopsin contain a membrane-bound subunit called an
**opsin** and a second small light-absorbing component called a **chromophore** .
The opsin of rods is **scotopsin** ; the opsins of cones are **photopsins** . The
chromophore of rods is a vitamin A–derived carotenoid called **retinal** . Thus,
an adequate intake of **vitamin A** is essential for normal vision.
Prolonged dietary deficiency of vitamin A leads to the inability to see in
dim light ( **night blindness** ).


**The interior of the discs of cones is continuous with the extracellular**

**space.**


The basic difference in the structure of the rod and cone discs—that is,
continuity with the plasma membrane—is correlated with the slightly different
means by which the visual pigments are renewed in rods and cones. Newly
synthesized rhodopsin is incorporated into the membrane of the rod disc as the
disc is being formed at the base of the outer segment. It then takes several days
for the disc to reach the tip of the outer segment. In contrast, although visual
proteins are constantly produced in retinal cones, the proteins are incorporated
into cone discs located anywhere in the outer segment.


**Vision is a process by which light striking the retina is converted into**
**electrical impulses that are transmitted to the brain.**


The impulses produced by light reaching the photoreceptor cells are conveyed
to the brain by an elaborate network of nerves. The conversion of the incident
light into electrical nerve impulses is called **visual processing** and involves
several steps:


A photochemical reaction occurs in the outer segment of the rods and cones.
In the dark, **rhodopsin** molecules contain a chromophore called retinal in
its isometric form of **11-** _**cis**_ **-retinal** . When rods are exposed to light, the 11_cis_ -retinal undergoes a conformational change from a bent to a more linear
molecule called **all** _**-trans-**_ **retinal** . The conversion of 11- _cis_ -retinal to all_trans_ -retinal activates opsin, which results in the release of all- _trans_ -retinal
into the rod’s cytoplasm (a reaction called **bleaching** ).
The activated **opsin** interacts with a G-protein called **transducin**, which
subsequently activates phosphodiesterase that breaks down **cyclic**
**guanosine monophosphate (cGMP)** . In the dark, high levels of cGMP
molecules produced in the photoreceptor cells by guanylyl cyclase are
bound to the cytoplasmic surface of **cGMP-gated Na** **[+]** **channels**, causing
them to stay open. Steady influx of Na [+] into the cells results in
**depolarization** of the plasma membrane and continuous **release of the**
**neurotransmitter (glutamate)** at the synaptic junction with the bipolar
neurons (Fig. 24.13).


**FIGURE 24.13.** **Schematic diagram of visual processing in the**
**photoreceptor cell. a.** In the dark, high levels of cGMP generated by


guanylyl cyclase are present in the cytoplasm of the rod. Some of the cGMP
molecules are bound to the cytoplasmic surface of cGMP-gated Na [+]

channels, causing them to stay open and resulting in continuous influx of Na [+]

and depolarization of the plasma membrane. This results in a steady release
of glutamate, a neurotransmitter, in the synaptic junctions with bipolar
neurons. Also in the dark, rhodopsin molecules that contain 11- _cis_ -retinal are
inactive. **b.** After exposure to light, 11- _cis_ -retinal undergoes a conformational
change to all- _trans_ -retinal. This conversion activates opsin (a reaction called
_bleaching_ ) and releases all- _trans_ -retinal into the rod’s cytoplasm. The
activated opsin interacts with G-protein, which subsequently activates
phosphodiesterase that breaks down cGMP, effectively lowering the
concentration of cGMP in the cell. In this condition, cGMP molecules
dissociate from Na [+] channels, resulting in their closing and hyperpolarization
of the plasma membrane. This results in a decrease in glutamate secretion,
which is detected by the bipolar neurons and conveyed as electrical
impulses to the brain. The released retinal from opsin is converted to its
original conformation in retinal pigment epithelial ( _RPE_ ) cells by the RPE65
enzymatic complex and is recycled to the photoreceptor cell. _cGMP_, cyclic
guanosine monophosphate; _GDP_, guanosine diphosphate; _GMP_, guanosine
monophosphate; _GTP_, guanosine triphosphate.


A decrease in the concentration of cGMP within the cytoplasm of the inner
segment of the photoreceptor cells is due to the action of phosphodiesterase.
Dissociation of cGMP from Na [+] channels effectively closes the channels
and reduces the influx of Na [+] into the cell, resulting in **hyperpolarization**
of the plasma membrane. The hyperpolarization causes a **decrease of**
**glutamate secretion** at the synapses with bipolar cells, which is detected
and conveyed as electrical impulses (see Fig. 24.13).


**Released retinal from opsin is converted back to its original**
**conformation in the RPE cells and Müller cells.**


After release, all- _trans_ -retinal is converted to all- _trans_ -retinol in the cytoplasm
of rods and cones and then transported to the cytoplasm of RPE cells (from
rods) or both RPE cells and Müller cells (from cones). The energy for this
process is provided by the mitochondria located in the inner segment of these
photoreceptors. Both Müller cells and RPE cells participate in a multistep
conversion of all- _trans_ -retinol to 11- _cis_ -retinal, which is transported back to
the photoreceptor cells for the resynthesis of rhodopsin. The **retinal pigment**
**epithelium–specific protein 65 kDa (RPE65)** is involved in this
conversion; thus, the visual cycle can begin again.

During the normal functioning of the photoreceptor cells, the membranous
discs of the outer segment are shed and phagocytosed by the pigment epithelial
cells (Fig. 24.14). It is estimated that each of these cells is capable of
phagocytosing and disposing of about 7,500 discs per day. The discs are


constantly turning over, and the production of new discs must equal the rate of
disc shedding.


**FIGURE 24.14.** **Electron micrograph of the retinal pigment epithelium in**
**association with the outer segments of rods and cones.** Retinal pigment
epithelial ( _RPE_ ) cells contain numerous elongated _melanin granules_ that are
aggregated in the apical portion of the cell, where the _microvilli_ extend from the
surface toward the outer segments of the rod and cone cells. The _retinal_
_pigment epithelial_ cells contain numerous mitochondria and _phagosomes_ . The
_arrow_ indicates the location of the junctional complex between two adjacent
cells. ×20,000. (Courtesy of Dr. Toichiro Kuwabara.) Discs are shed from both
rods and cones.


In rods, after a period of sleep, a burst of **disc shedding** occurs as light first
enters the eye. The time of disc shedding in cones is more variable. The
shedding of discs in cones also enables the receptors to eliminate superfluous
membrane. Although not fully understood, the shedding process in cones also
alters the size of the discs so that the conical form is maintained as discs are

released from the distal end of the cone.


**The outer limiting membrane (layer 3) is formed by a row of zonulae**
**adherentes between Müller cells.**


The **outer limiting membrane** is not a true membrane. It is a row of zonulae
adherentes that attaches the apical ends of Müller cells (i.e., the end that faces
the pigment epithelium) to each other and to the rods and cones (see Fig.
24.9). Because Müller cells end at the base of the inner segments of the
receptors, they mark the location of this layer. Thus, the supporting processes
of Müller cells, on which the rods and cones rest, are pierced by the inner and
outer segments of the photoreceptor cells. This layer is thought to be a


metabolic barrier that restricts the passage of large molecules into the inner
layers of the retina.


**The outer nuclear layer (4) contains the nuclei of the retinal rods and**

**cones.**


The region of the rod cytoplasm that contains the nucleus is separated from the
inner segment by a tapering process of the cytoplasm. In cones, the nuclei are
located close to the outer segments, and no tapering is seen. The cone nuclei
stain lightly and are larger and more oval than rod nuclei. Rod nuclei are
surrounded by only a thin rim of cytoplasm. In contrast, a relatively thick
investment of cytoplasm surrounds the cone nuclei (see Fig. 24.10).


**The outer plexiform layer (5) is formed by the processes of the**
**photoreceptor cells and neurons.**


The **outer plexiform layer** is formed by the processes of retinal rods and
cones and the processes of horizontal, interplexiform, amacrine, and bipolar
cells. The processes allow the electrical coupling of photoreceptor cells to
these specialized interneurons via synapses. A thin process extends from the
region of the nucleus of each rod or cone to an inner expanded portion with
several lateral processes. The expanded portion is called a **spherule** in a rod
and a **pedicle** in a cone. Normally, many photoreceptor cells converge onto
one bipolar cell and form interconnecting neural networks. Cones located in
the fovea, however, synapse with a single bipolar cell. The fovea is also unique
in that the compactness of the inner neural layers of the retina causes the
photoreceptor cells to be oriented obliquely. Horizontal cell dendritic
processes synapse with photoreceptor cells throughout the retina and further
contribute to the elaborate neuronal connections in this layer.


**The inner nuclear layer (6) consists of the nuclei of horizontal,**
**amacrine, bipolar, interplexiform, and Müller cells.**


**Müller cells** form the scaffolding for the entire retina. Their processes invest
the other cells of the retina so completely that they fill most of the extracellular
space. The basal and apical ends of Müller cells form the inner and outer
limiting membranes, respectively. Microvilli extending from their apical
border lie between the photoreceptor cells of the rods and cones. Capillaries
from the retinal vessels extend only to this layer. The rods and cones carry out
their metabolic exchanges with extracellular fluids transported across the
blood–retina barrier of the RPE.

The four types of conducting cells—bipolar, horizontal, interplexiform,
and amacrine—found in this layer have distinct orientations (see Fig. 24.9):


**Bipolar cells** and their processes extend to both the inner and outer
plexiform layers. In the peripheral regions of the retina, the axons of bipolar


cells pass to the inner plexiform layer where they synapse with several
ganglion cells. Through these connections, the bipolar cells establish
communication with multiple cells in each layer, except in the fovea, where
they may synapse only with a single ganglion cell to provide greater visual
acuity in this region.
**Horizontal cells** and their processes extend to the outer plexiform layer
where they intermingle with processes of bipolar cells. The cells have
synaptic connections with rod spherules, cone pedicles, and bipolar cells.
This electrical coupling of cells is thought to affect the functional threshold
between rods and cones and bipolar cells.
**Amacrine cells’** processes pass inward, contributing to a complex
interconnection of cells. Their processes branch extensively to provide sites
of synaptic connections with axonal endings of bipolar cells and dendrites
of ganglion cells. Besides bipolar and ganglion cells, the amacrine cells
synapse in the inner plexiform layer with interplexiform and other amacrine
cells (see Fig. 24.9).
**Interplexiform cells** and their processes have synapses in both inner and
outer plexiform layers. These cells convey impulses from the inner
plexiform to the outer plexiform layer.


**The inner plexiform layer (7) consists of a complex array of**
**intermingled neuronal cell processes.**


The **inner plexiform layer** consists of synaptic connections between axons of
the bipolar neurons and dendrites of ganglion cells. It also contains synapses
between intermingling processes of amacrine cells and bipolar neurons,
ganglion cells, and interplexiform neurons. The course of these processes is
parallel to the inner limiting membrane, thus giving the appearance of
horizontal striations to this layer (see Fig. 24.9).


**The ganglion cell layer (8) consists of the cell bodies of large**
**multipolar neurons.**


The cell bodies of large **multipolar nerve cells**, measuring as much as 30 μm
in diameter, constitute the ganglion cell layer. These nerve cells have lightly
staining round nuclei with prominent nucleoli and Nissl bodies in their
cytoplasm. An axonal process emerges from the rounded cell body, passes into
the **nerve fiber layer**, and then enters **the optic nerve** . The dendrites extend
from the opposite end of the cell to ramify in the inner plexiform layer. In the
peripheral regions of the retina, a single ganglion cell may synapse with 100
bipolar cells. In marked contrast, in the macular region surrounding the fovea,
the bipolar cells are smaller (some authors refer to them as _midget bipolar_
_cells_ ), and they tend to make one-to-one connections with ganglion cells. Over
most of the retina, the ganglion cells are only a single layer of cells. At the


macula, however, they are piled as many as eight deep, although they are
absent over the fovea itself. Scattered among the ganglion cells are small
neuroglial cells with densely staining nuclei (see Fig. 24.9).


**The layer of optic nerve fibers (9) contains axons of the ganglion**
**cells.**


The axonal processes of the ganglion cells form a flattened layer running
parallel to the retinal surface. This layer increases in depth as the axons
converge at the **optic disc** (Fig. 24.15). The axons are thin, nonmyelinated
processes measuring as much as 5 μm in diameter (see Fig. 24.9). The retinal
vessels, including the superficial capillary network, are primarily located in
this layer.


**FIGURE 24.15.** **Normal view of the fundus in ophthalmoscopic**
**examination of the right eye.** The site where the axons converge to form the
optic nerve is called the _optic disc_ . Because the optic disc is devoid of
photoreceptor cells, it is a blind spot in the visual field. From the center of the
optic nerve (clinically called the _optic cup_ ), _central retinal vessels_ emerge. The
artery divides into upper and lower branches, each of which further divides into
nasal and temporal branches (note the nasal and temporal directions on the
image). Veins have a similar pattern of tributaries. Approximately 17 degree or
2.5 times optic disc diameters lateral to the disc, the slightly oval-shaped, blood
vessel–free, and pigmented area represents the macula lutea. The _fovea_
_centralis_, a shallow depression in the center of the _macula lutea_, is also visible.


(Courtesy of Dr. Renzo A. Zaldivar.) The inner limiting membrane (layer 10)
consists of a basal lamina separating the retina from the vitreous body.


The **inner limiting membrane** forms the innermost boundary of the retina. It
serves as the basal lamina of Müller cells (see Fig. 24.9). In younger
individuals, reflections from the internal limiting membrane produce a
**retinal sheen** that is seen during ophthalmoscopic examination of the
eye. In older individuals, a semitranslucent sheet of cells and
extracellular matrix can be formed on the inner surface of the retina in
conjunction with the inner limiting membrane. This condition is called
**epiretinal membrane (ERM)** or **macular pucker** and is responsible for
variable clinical symptoms, including optical distortion and blurred
vision. ERM is initially formed by cells from within the retina (RPE cells,
Müller cells, and astrocytes) that begin proliferating and migrating onto
the surface of the internal limiting membrane. Later, the membrane is
infiltrated by macrophages, fibroblasts, and myofibroblasts. To prevent
damage to the underlying retina, surgical removal of the ERM may be
performed.

##### **Specialized regions of the retina**


The **fovea (fovea centralis)** appears as a small (1.5 mm in diameter),
shallow depression located at the posterior pole of the visual axis of the eye.
Its central region, known as the **foveola**, is about 200 μm in diameter (see Fig.
24.15). Except for the photoreceptor layer, most of the layers of the retina are
markedly reduced or absent in this region (see Fig. 24.6). Here, the
photoreceptor is composed entirely of cones (~4,000) that are longer and more
slender and rod like than they are elsewhere. The fovea is the area of the retina
specialized for the discrimination of details and color vision. The ratio
between cones and ganglion cells is close to 1:1. Retinal vessels are absent in
the fovea, allowing light to pass unobstructed into the cones’ outer segments.
The adjacent pigment epithelial cells and choriocapillaris are also thickened in
this region.

The **macula lutea** is the area surrounding the fovea and is approximately
5.5 mm in diameter. It is yellowish because of the presence of yellow pigment
(xanthophyll). The macula lutea contains approximately 17,000 cones and
gains rods at its periphery. Retinal vessels are also absent in this region. Here,
the retinal cells and their processes, especially the ganglion cells, are heaped
up on the sides of the fovea so that light may pass unimpeded to this most
sensitive area of the retina.

##### **Vessels of the retina**


The **central retinal artery** and **central retinal vein**, the vessels that can be
seen and assessed with an ophthalmoscope, pass through the center of the


optic nerve to enter the bulb of the eye at the optic disc (see Fig. 24.2 and
pages 982-983, the section on the development of the eye). The central retinal
artery provides nutrients to the inner retinal layers. The artery branches
immediately into the upper and lower branches, each of which divides again
into nasal and temporal branches (see Fig. 24.15). Veins undergo a similar
pattern of branching. The vessels initially lie between the vitreous body and
the inner limiting membrane. As the vessels pass laterally, they also move
deeper within the inner retinal layers. Branches from these vessels form a
capillary plexus that reaches the inner nuclear layer and, therefore, provides
nutrients to the inner retinal layers (layers 6–10; see pages 993-994). Nutrients
to the remaining layers (layers 1–5) are provided by diffusion from the
vascular choriocapillary layer of the choroid. The branches of the **central**
**retinal artery** do not anastomose and, therefore, are classified as
**anatomic end arteries** . Evaluation of the retinal vessels and
appearance of the optic disc during ophthalmoscopy not only gives
important information on the state of the eye but also may reveal early
clinical signs of a number of conditions, including increased
**intracranial pressure**, **hypertension**, **glaucoma**, and **diabetes** .

### **Crystalline Lens**


**Like the lens in a camera, the basic function of the eye lens is to**
**transmit and focus light onto the retina.**


The **lens** is a transparent, biconvex structure that has no vessels or nerves and
is almost totally devoid of connective tissue, except for an enveloping capsule
of basal lamina. It is suspended between the edges of the ciliary body by the
**zonular fibers** . The pull of the zonular fibers keeps the lens in a flattened
condition. Release of tension causes the lens to widen or **accommodate** to
bend light rays originating close to the eye so that they focus on the retina.


The lens has three principal components (Fig. 24.16):


**FIGURE 24.16.** **Structure of the lens. a.** This schematic drawing of the lens
suspended from ciliary processes by zonular fibers indicates its structural
components. Note that the capsule of the lens is formed by the basal lamina of
the lens fibers and the subcapsular epithelium located on the anterior surface
of the lens. A strip of capsule was removed on this drawing to show underlying
epithelium. Also note the location of the germinal zone ( _yellow_ ) at the lens
equator, where cells divide and differentiate into the lens fiber cells. The
organelle-free center of the lens is occupied by the lens nucleus. **b.** This highmagnification photomicrograph of the germinal zone of the lens (near its
equator) shows the active process of lens fiber formation from the _subcapsular_
_epithelium_ . Note the thick _lens capsule_ and the underlying layer of nuclei of
lens fibers during their differentiation. The _mature lens fibers_ do not possess
nuclei. ×570.


The **lens capsule** is a thick basal lamina that surrounds the outer surface of
the lens. It originates as the basal lamina of the embryonic lens vesicle. The
anterior part of the capsule is thick, measuring approximately 10–20 μm,
and is produced by the anterior lens cells. The posterior part of the capsule
is much thinner, measuring approximately 5–10 μm. The lens capsule,
composed primarily of type IV collagen and proteoglycans (i.e., laminin,
entactin, perlecan), is elastic. It is thickest at the equator where the zonular
fibers attach to it.
The **subcapsular epithelium** is derived from the epithelial cells of the
anterior part of the embryonic lens vesicle. It represents a single cuboidal
layer of **lens epithelial cells** present only on the anterior surface of the
lens. The epithelial cells of the posterior part of the vesicle elongate


anteriorly and form the **primary lens fibers** that fill the cavity of the optic
vesicle.
**Secondary lens fibers (lens fiber cells)** are formed at the periphery near
the **lens equator** . Here, epithelial cells proliferate and migrate along the
posterior lens capsule to differentiate into mature lens fiber cells. In the
center of the lens, epithelial cells are quiescent. As lens fiber cells
differentiate, they undergo massive elongation and lose all of their
organelles, including nuclei, forming the **organelle-free zone** .


**Gap junctions** connect the cuboidal cells of the subcapsular epithelium.
They have few cytoplasmic organelles and stain faintly. The apical region of
the cell is directed toward the internal aspect of the lens and the **lens fibers**,
with which they form **junctional complexes** . The lens increases in size
during normal growth and then continues to produce new lens fibers at an
ever-decreasing rate throughout life. The new lens fibers develop from the
subcapsular epithelial cells located near the equator (see Fig. 24.16) are laid
down peripherally as concentric lamellae in an onion-like arrangement. Cells
in this region increase in height and then differentiate into lens fibers.

As the lens fibers develop, they become highly elongated and appear as
thin, flattened structures. They lose their nuclei and other organelles as they
become filled with proteins called **crystallins** . Mature lens fibers attain a
length of 7–10 mm, a width of 8–10 μm, and a thickness of 2 μm. In the adult
lens, only lens fibers in the outermost region maintain their nuclei and
organelles. Near the center, in the **lens nucleus**, the fibers are compressed
and condensed to such a degree that individual fibers are impossible to
recognize. The lens nucleus is an organelle-free zone and is composed of
primary lens fiber cells laid down during embryonic and fetal development.
The lens fibers are joined at their apical and basal ends by specialized
junctions called **sutures** . Despite its density and protein content, the lens is
normally transparent (see Fig. 24.16). The high density of lens fibers makes it
difficult to obtain routine histologic sections of the lens that are free from
artifacts.


**Changes in the lens are associated with aging.**


With increasing age, the lens gradually loses its elasticity and ability to
accommodate. This condition, called **presbyopia**, usually occurs in the
fourth decade of life. It is easily corrected by wearing reading glasses
or using a magnifying lens.

Loss of transparency of the lens or its capsule is also a relatively
common condition associated with aging. This condition, called
**cataract**, may be caused by conformational changes or cross-linking of
proteins. The development of a cataract may also be related to disease
processes, metabolic or hereditary conditions, trauma, or exposure to a


deleterious agent (such as ultraviolet radiation). Cataracts that
significantly impair vision can usually be corrected surgically by
removing the lens and replacing it with a plastic lens implanted in the
posterior chamber.

### **Vitreous Body**


**The vitreous body is the transparent jelly-like substance that fills the**
**vitreous chamber in the posterior segment of the eye.**


The **vitreous body** is loosely attached to the surrounding structures, including
the inner limiting membrane of the retina. The main portion of the vitreous
body is a homogeneous gel containing approximately 99% water (the vitreous
humor), collagen, glycosaminoglycans (principally hyaluronan), and a small
population of cells called **hyalocytes** . These cells are believed to be
responsible for the synthesis of collagen fibrils and glycosaminoglycans.
Hyalocytes in routine H&E preparations are difficult to visualize. Often, they
exhibit a well-developed rER and Golgi apparatus. Fibroblasts and tissue
macrophages are sometimes seen in the periphery of the vitreous body. The
**hyaloid canal** (or **Cloquet canal** ), which is not always visible, runs through
the center of the vitreous body from the optic disc to the posterior lens capsule.
It is the remnant of the pathway of the hyaloid artery of the developing eye.

### **ACCESSORY STRUCTURES OF THE EYE**


**The primary functions of the eyelids are to cover, protect, and**
**lubricate the eyes.**


The **eyelids** represent folds of modified skin containing highly modified
epidermal appendages to cover, protect, and lubricate the anterior portions of
the eyes. The anterior surface of the eyelid is covered by thin **skin**, and its
posterior surface is lined by a specialized mucous membrane, the
**conjunctiva** . The skin of the eyelids is loose and elastic to accommodate their
movement. Within each eyelid is a flexible support, the **tarsal plate**,
consisting of dense fibrous and elastic tissue. In the upper eyelid, the lower
free edge of the tarsal plate extends to the lid margin, and its superior border
serves for the attachment of smooth muscle fibers of the **superior tarsal**
**muscle (of Müller)** . The undersurface of the tarsal plate is covered by the
conjunctiva (Fig. 24.17). The striated **orbicularis oculi muscle**, a facial
expression muscle, forms a thin oval sheet of circularly oriented skeletal
muscle fibers overlying the tarsal plate. In addition, the connective tissue of
the upper eyelid contains tendon fibers of the **levator palpebrae superioris**
**muscle** that open the eyelid (see Fig. 24.17). A mucocutaneous junction


between eyelid skin and conjunctiva occurs near the lid margin. The
**eyelashes** emerge from the most anterior edge of the lid margin. They are
short, stiff, curved hairs and may occur in double or triple rows. The lashes on
the same eyelid margin may have different lengths and diameters.


**FIGURE 24.17.** **Structure of the eyelid. a.** This schematic drawing of the
eyelid shows the skin, associated skin appendages, muscles, tendons,
connective tissue, and conjunctiva. Note the distribution of multiple small
glands associated with the eyelid and observe the reflection of the palpebral
conjunctiva in the fornix of the lacrimal sac to become the bulbar conjunctiva. **b.**
Photomicrograph of a sagittal section of the eyelid stained with picric acid for
better visualization of epithelial components of the skin and the numerous
glands. In this preparation, muscle tissue (i.e., _orbicularis oculi muscle_ ) stains
_yellow_, and the epithelial cells of the skin, conjunctiva, and glandular epithelium
are _green_ . Note the presence of numerous glands within the eyelid. The _tarsal_
_(Meibomian) gland_ is the largest gland, and it is located within the dense
connective tissue of the tarsal plates. This sebaceous gland secretes into ducts
opening onto the eyelids. ×20. **Inset.** Higher magnification of a tarsal gland
from the _boxed area_ showing the typical structure of a holocrine gland. ×60.


**The conjunctiva lines the space between the inner surface of the**
**eyelids and the anterior surface of the eye without covering the**

**cornea.**


The **conjunctiva** is a thin, transparent mucous membrane that extends from
the corneoscleral limbus located on the peripheral margin of the cornea across
the sclera ( **bulbar conjunctiva** ) and covers the internal surface of the eyelids
( **palpebral conjunctiva** ). The palpebral conjunctiva merges with the bulbar


conjunctiva at the fornices of the conjunctival sac; this part is called the
**forniceal conjunctiva** (Fig. 24.18). Bulbar, palpebral, and forniceal
conjunctiva form a conjunctival sac, a space between the eyelid and eyeball
that opens anteriorly at the palpebral fissure. The conjunctival sac can hold
fluid up to 30 µL. Because a standard eyedropper dispenses about 50
µL of suspended medicine per drop, one drop is more than enough to
overfill the conjunctival sac.


**FIGURE 24.18.** **Conjunctiva and conjunctival sac.** This photograph of the
lower part of the eyeball with a reflected lower eyelid shows different regions of
the conjunctiva that line the conjunctival sac. The area shown is located
between the inner surface of the eyelid and the anterior surface of the eye. The
bulbar conjunctiva extends from the corneoscleral limbus covering the sclera of
the eye (it does not cover the cornea) to its reflections onto the internal surface
of the eyelid, at which point it is called the _palpebral conjunctiva_ . This
photograph shows the inferior point of reflection onto the lower eyelid (called
the _inferior fornix_ of the conjunctival sac). The conjunctiva in these regions is
recognized as the forniceal conjunctiva.


The conjunctiva consists of a **stratified columnar epithelium** containing
numerous **goblet cells** and rests on a lamina propria composed of loose
connective tissue. The goblet cells secrete a component of the tears that bathe
the eye. Melanocytes are present in the basal epithelial layer and, like
melanocytes in the skin, transfer melanosomes into neighboring epithelial
cells. Accumulation of diffuse lymphatic tissue is evident, especially deep to


the forniceal conjunctiva (Fig. 24.19). These specialized collections of T and B
lymphocytes underlying the conjunctiva are called **conjunctiva-associated**
**lymphatic tissue (CALT)** (Fig. 24.20). It functions to recognize and process
antigens and trigger an appropriate immune response against the microbial
invasion of the ocular surface. The conjunctiva is supplied with blood by the
branches of arteries of the eyelid (marginal tarsal arcades) and from the
eyeball (anterior ciliary arteries). The conjunctiva receives sensory innervation
from the branches of the trigeminal nerve. **Conjunctivitis**, an inflammation
of the conjunctiva, commonly called **pinkeye**, is characterized by
redness, irritation, and watering of the eyes. For more clinical
information about this condition, see Folder 24.6.


**FIGURE 24.19.** **Superior fornix of the conjunctival sac.** This lowmagnification hematoxylin and eosin (H&E)-stained specimen was obtained
from the superior fornix of the conjunctival sac as indicated by the _rectangle_ in
the inset. The palpebral conjunctiva lines the inner surface of the eyelid, and in
the superior fornix of the conjunctival sac, it reflects onto the eyeball (bulbar
conjunctiva). This reflection is identified as the forniceal conjunctiva and is
composed of stratified columnar epithelium containing numerous goblet cells.
Accumulations of lymphatic tissue called _conjunctiva-associated lymphatic_
_tissue_ ( _CALT_ ) are clearly visible. There are numerous blood vessels ( _BV_ )
underlying the palpebral conjunctiva. ×120. (Courtesy of Dr. Nick Mamalis,


University of Utah, Moran Clinical Ophthalmology Resource for Education

[CORE], Salt Lake City, Utah.)


**FIGURE 24.20.** **Forniceal conjunctiva.** This high-magnification hematoxylin
and eosin (H&E)-stained specimen shows the fornix of the conjunctival sac.
The forniceal conjunctiva shows a typical pattern of the stratified columnar
epithelium containing goblet cells that rests on a lamina propria composed of
loose connective tissue. The stratified columnar epithelium farther away from
the fornix may change into columnar stratified or squamous stratified
nonkeratinized epithelium ( _lower right corner of conjunctival sac_ ). Note the
accumulations of diffuse lymphatic tissue deep into the conjunctiva known as
_conjunctiva-associated lymphatic tissue_ ( _CALT_ ). ×220. (Courtesy of Dr. Nick
Mamalis, University of Utah, Moran Clinical Ophthalmology Resource for
Education [CORE], Salt Lake City, Utah.) FOLDER 24.6

##### **CLINICAL CORRELATION: CONJUNCTIVITIS**


**Conjunctivitis**, otherwise known as pinkeye, is an inflammation of the
conjunctiva. It may be localized in either the palpebral conjunctiva or the
bulbar conjunctiva. Individuals may present with relatively nonspecific
symptoms and signs that include redness, irritation, and watery discharge
from the eye (Fig. F24.6.1). The symptoms can also mimic a foreign-body
sensation. Extended use of contact lenses can cause allergic or bacterial
conjunctivitis and may be the first sign of more serious ocular disease (i.e.,
corneal ulcer). In general, symptoms that last <4 weeks are classified as


**acute conjunctivitis**, and those extending for a longer period are
referred to as **chronic conjunctivitis** .


**FIGURE F24.6.1.** **Conjunctivitis.** This photograph of the lower part of the eyeball
with reflected lower eyelid shows an infected conjunctiva. The enlarged blood
vessels of the conjunctiva are responsible for moderate redness of the eye with
conjunctival swelling. Moderately, clear (in allergic conjunctivitis) or purulent (in
bacterial conjunctivitis) discharge is visible. (Courtesy of Dr. Renzo A. Zaldivar.)
Acute conjunctivitis is most commonly caused by bacteria; a variety of viruses,
including HIV, varicella-zoster virus (VZV), and herpes simplex virus (HSV); or
allergic reactions. Bacterial conjunctivitis often causes an opaque purulent
discharge containing white cells and desquamated epithelial cells. On eye
examination, the purulent discharge and conjunctival papillae help differentiate
between bacterial and viral etiology. Viral conjunctivitis is most common in adults.
Clinically, it presents as a diffuse pinkness of the conjunctiva with particularly
numerous lymphoid follicles on the palpebral conjunctiva, often accompanied by
enlarged preauricular lymph nodes. Viral conjunctivitis is very contagious and
usually associated with a recent upper respiratory infection. Patients need to be
advised to avoid touching their eyes, to wash their hands frequently, and to avoid
sharing towels and washcloths.


Bacterial conjunctivitis is usually treated with antibiotic eye drops or
ointments. For viral conjunctivitis, no antimicrobial therapy is needed.
However, conservative management with artificial tears to keep the eye
lubricated may relieve symptoms. For severe cases, topical corticosteroid
drops may be prescribed to reduce the discomfort of inflammation.
However, prolonged use of corticosteroid drops increases the risk of side
effects. Antibiotic drops may also be used for the treatment of secondary


infections. Viral conjunctivitis usually resolves within 3 weeks. However, in
the worst cases, it may take more than a month.


**Secretions from modified glands in the eyelid provide additional**
**protection to the eye.**


In addition to eccrine sweat glands, which discharge their secretions directly
onto the skin, the eyelid contains four other major types of glands (see Fig.
24.17):


The **tarsal glands (Meibomian glands)**, long sebaceous glands embedded
in the tarsal plates, appear as vertical yellow streaks in the tissue deep into
the conjunctiva. Their elongated ducts open at the lid margin behind rows of
eyelashes. About 25 tarsal glands are present in the upper eyelid, and 20 are
present in the lower eyelid. The sebaceous secretion of the tarsal glands
produces an oily layer on the surface of the tear film that retards the
evaporation of the normal tear layer. Blockage of the tarsal gland
secretion leads to **chalazion** (tarsal gland lipogranuloma), an
inflammation of the tarsal gland. It presents as a painless cyst usually
on the upper eyelid that disappears after a few months without
therapeutic intervention.
**Sebaceous glands of eyelashes (glands of Zeis)** are small, modified
sebaceous glands that are connected with and empty their secretion into the
follicles of the eyelashes. Bacterial infection of these sebaceous glands
causes a **stye** (also called a **hordeolum** ), a painful tenderness and
redness of the affected area of the eyelid.
**Apocrine glands of eyelashes (glands of Moll)** are small sweat glands
with unbranched sinuous tubules that begin as a simple spiral.
**Accessory lacrimal glands** are compound serous tubuloalveolar glands
that have distended lumina. They are located on the inner surface of the
upper eyelids ( **glands of Wolfring** ) and in the fornix of the conjunctival
sac ( **glands of Krause** ).


All glands of the human eyelid are innervated by neurons of the autonomic
nervous system, and their secretion is synchronized with the lacrimal glands
by a common neurotransmitter, vasoactive intestinal polypeptide (VIP).


**The lacrimal gland produces tears that moisten the cornea and flow to**
**the nasolacrimal duct.**


Tears are produced by the **lacrimal glands** and, to a lesser degree, by the
accessory lacrimal glands. The lacrimal gland is located beneath the
conjunctiva on the upper lateral side of the orbit (Fig. 24.21). The lacrimal
gland consists of several separate lobules of tubuloacinar serous glands. The


acini have large lumina lined with columnar cells. Myoepithelial cells, located
below the epithelial cells within the basal lamina, aid in the release of tears
(Fig. 24.22). Approximately 12 ducts drain from the lacrimal gland into the
reflection of conjunctiva just beneath the upper eyelid, known as the **fornix of**
**the conjunctival sac** .


**FIGURE 24.21.** **Schematic diagram of the eye and lacrimal apparatus.** This
drawing shows the location of the lacrimal gland and components of the
lacrimal apparatus, which drains the lacrimal fluid into the nasal cavity.


**FIGURE 24.22.** **Photomicrograph of lacrimal gland.** The lacrimal gland
consists of tubuloacinar serous secretory units. The acini are lined with serous
secretory columnar cells. Myoepithelial cells ( _MEp_ ) are present below the
epithelial cells within the basal lamina. Cytoplasm of the secretory cells
contains small lipid droplets and mucin-containing granules. Intralobular ducts
( _D_ ) lined by serous cells also contain myoepithelial cells. Occasional plasma
cells ( _P_ ) and lymphocytes are present between acini of the lacrimal gland. _BV_,
blood vessels. ×450.


Tears drain from the eye through **lacrimal puncta**, the small openings of
the **lacrimal canaliculi**, located at the medial angle. The upper and lower
canaliculi join to form the **common canaliculus**, which opens into the
lacrimal sac. The sac is continuous with the **nasolacrimal duct**, which opens
into the nasal cavity below the inferior nasal conchae. A pseudostratified
ciliated epithelium lines the lacrimal sac and the nasolacrimal duct.
**Dacryocystitis** is an inflammation of the lacrimal sac that is frequently
caused by an obstruction of the nasolacrimal duct. It can be acute,
chronic, or congenital. It usually affects older individuals and is most
often secondary to stenosis (narrowing) of the lacrimal canaliculi.


**Tears protect the corneal epithelium and contain antibacterial and UV-**
**protective agents.**


**Tears** keep the conjunctiva and corneal epithelium moist and wash foreign
material from the eye as they flow across the corneal surface toward the medial
angle of the eye (see Fig. 24.21). The thin film of tears covering the corneal
surface is not homogeneous but a mixture of products secreted by the lacrimal
glands, the accessory lacrimal glands, the goblet cells of the conjunctiva, and
the tarsal glands of the eyelid. The tear film contains proteins (tear albumins
and lactoferrin), enzymes (lysozyme), lipids, metabolites, electrolytes, and
medications, the latter secreted during therapy.

The tear cationic protein lactoferrin increases the activity of various natural
antimicrobial agents, such as lysozyme.


**The eye is moved within the orbit by coordinated contraction of**
**extraocular muscles.**


Six muscles of the eyeball (also called **extraocular** or **extrinsic muscles** )
attach to each eye. These are the medial, lateral, superior, and inferior rectus
muscles and the superior and inferior oblique muscles. The superior oblique
muscle is innervated by the trochlear nerve (cranial nerve IV). The lateral
rectus muscle is innervated by the abducens nerve (cranial nerve VI). All of
the remaining extraocular muscles are innervated by the oculomotor nerve
(cranial nerve III). The combined, precisely controlled action of these muscles
allows vertical, lateral, and rotational movement of the eye. Normally, the
actions of the muscles of both eyes are coordinated so that the eyes
move in parallel (called **conjugate gaze** ).

## EYE


**OVERVIEW OF THE EYE**


The **eye** is a paired, specialized sensory organ that provides the sense of
sight.
The tissues of the eye are derived from **neuroectoderm** (retina),
**surface ectoderm** (lens, corneal epithelium), and **mesoderm** (sclera,
corneal stroma, vascular coat).
The eyeball is composed of three structural layers: the outer
**corneoscleral (fibrous) coat** consisting of the transparent cornea and


the opaque white sclera; the middle **vascular coat** consisting of the
choroid, ciliary body, and iris; and the inner layer, the **retina** .
The layers of the eye and the lens serve as boundaries for three chambers:
the **anterior chamber** and **posterior chamber**, which are filled with
**aqueous humor**, and the **vitreous chamber**, which is occupied by a
transparent gel, the **vitreous body** .
**Aqueous humor** is secreted by the ciliary processes into the posterior
chamber. From there it flows through the pupil into the anterior chamber,
where it drains inside the **iridocorneal angle** to the **scleral venous**
**sinus (canal of Schlemm)** .


**COATS IN THE WALL OF THE EYE**


The **cornea**
is transparent and consists of five layers (beginning from the
anterior surface): **corneal** **epithelium** (nonkeratinized stratified
squamous epithelium), **Bowman membrane** (anterior basement
membrane for corneal epithelium), a thick avascular **corneal stroma**,
**Descemet membrane** (posterior basement membrane for corneal
endothelium), and **corneal endothelium** .
The **sclera** is opaque and consists predominantly of dense connective
tissue. It communicates with the cornea at the **corneoscleral limbus**,
which contains **corneolimbal stem cells** .
The **iris** arises from the ciliary body, and the diameter of its opening
( **pupil** ) is controlled by smooth muscle fibers of the **sphincter pupillae**
**muscle** and the myoepithelial cell layer of the **dilator pupillae muscle** .
Its posterior surface is covered by pigment epithelium and contains a
stroma that is abundant with melanocytes.
The **ciliary body** is located between the iris and the choroid. It contains
**ciliary processes** that secrete aqueous humor, anchors **zonular fibers**
that suspend the lens, and contains **ciliary muscle** that alters the shape of
the lens during **lens accommodation** .
The **lens** is a transparent, avascular, biconvex structure that is suspended
between the edges of the ciliary body. It consists of a **lens capsule**,
**subcapsular epithelium**, and **lens fiber cells** .
The **choroid** is part of the vascular coat and has an inner
**choriocapillary layer** containing blood vessels that provide nutrients to
the retina and an outer **Bruch membrane** that serves as the basal lamina

for both the endothelial and RPE cells.

The **retina** is derived from the inner and outer layers of the optic cup. It
consists of two basic layers: the **neural retina** is the inner layer
containing photoreceptor cells, and the **retinal pigment epithelium**
**(RPE)** is the outer layer that attaches to the choroid.


**RETINA**


The **retina** contains 10 layers of cells and their processes. Major cells in
the retina include **photoreceptors** (rods and cones), **conducting**
**neurons** (bipolar neurons and ganglion cells), **association neurons**,
and **supporting cells** (e.g., Müller cells).
**Retinal pigment epithelium** (layer 1) is the outermost layer of the
retina and **absorbs scattered light**, contributes to the **blood–retina**
**barrier,** **restores** **photosensitivity** to visual pigments, and
**phagocytoses membranous discs** from the rods and cones.
**Rods** (layer 2) are most numerous (120 million) in the retina and detect
light intensity with their cylindrical outer segments. **Cones** (layer 2) are
less numerous (7 million) and, with their conical outer segment, detect
three different wavelengths of light corresponding to the primary colors:
blue, green, and red.
Rods contain the visual pigment **rhodopsin** that consists of **opsin** and a
small light-absorbing compound, **retinal** . Cone cells contain the visual
pigment **iodopsin** .
Conversion of light into nerve impulses in the photoreceptors is called
**visual processing** . It involves a photochemical reaction based on the
conversion of **11-cis-retinal** into **all-trans-retinal** in the rhodopsin. This
results in the activation of opsin, which, in turn, activates G-protein and
initiates hyperpolarization of the photoreceptor cell membrane that is
detected by the bipolar neurons as a nerve impulse.
The **outer limiting membrane** (layer 3) is formed by a row of zonulae
adherentes between Müller cells.

The **outer nuclear layer** (layer 4) contains the nuclei of rods and cones,
and the **outer plexiform layer** (layer 5) contains their processes, which
synapse with the horizontal, amacrine, and bipolar cells (the nuclei of
which reside in the **inner nuclear layer** [layer 6]).
Axons from cells in the outer plexiform layer synapse in the **inner**
**plexiform layer** (layer 7) with ganglion cells, the cell bodies of which
reside in the **ganglion cell layer** (layer 8). These cells send axons to the
**layer of optic nerve fibers** (layer 9), which forms the optic nerve.
The **inner limiting membrane** (layer 10) consists of a basal lamina
separating the retina from the vitreous body.


**ACCESSORY STRUCTURES OF THE EYE**


The **eyelids** consist of skin, tarsal plates, part of the **orbicularis oculi**
**muscle**, tendon fibers of the **levator palpebrae superioris muscle** (in
the upper eyelid), and the palpebral conjunctiva.


The **conjunctiva** consists of **stratified columnar epithelium** with
**goblet cells** . It lines the space between the inner surface of the eyelid
and the anterior surface of the eye lateral to the cornea.
A diffuse lymphatic tissue called **conjunctiva-associated lymphatic**
**tissue (CALT)** is underlying conjunctiva at the superior and inferior
fornices of the conjunctival sac.
The **tarsal glands (Meibomian glands)** are long sebaceous glands
embedded in the tarsal plates of the upper and lower eyelids.
The **lacrimal gland** produces tears that moisten the cornea and flow to
the nasolacrimal duct and into the nasal cavity.




##### Modified drawing of human eye, meridional perspective by E. Sobotta.

The innermost layer is the **retina** ( _R_ ), which consists of several
layers of cells. Among these are receptor cells (rods and cones),
neurons (e.g., bipolar and ganglion cells), supporting cells, and a
pigment epithelium (see Plate 24.2, page 1012). The receptor components of the retina
are situated in the posterior three-fifths of the eyeball. At the anterior boundary of the
receptor layer, the **ora serrata** ( _OS_ ), the retina becomes reduced in thickness, and
nonreceptor components of the retina continue forward to cover the posterior or inner
surface of the **ciliary body** ( _CB_ ) and the **iris** ( _I_ ). This anterior nonreceptor extension


of the inner layer is highly pigmented, and the pigment (melanin) is evident as the
black inner border of these structures.


The **uvea**, the middle layer of the eyeball, consists of the choroid, the ciliary body,
and the iris. The choroid is a vascular layer; it is relatively thin and difficult to
distinguish in the accompanying figure, except by location. On this basis, the **choroid**
( _Ch_ ) is identified as being just external to the pigmented layer of the retina. It is also
highly pigmented; the choroidal pigment is evident as a discrete layer in several parts
of the section.


Anterior to the ora serrata, the uvea is thickened; here, it is called the ciliary body
( _CB_ ). This contains the ciliary muscle (see Plate 24.3, page 1014), which brings about
adjustments of the lens to focus light. The ciliary body also contains processes to which
the zonular fibers are attached. These fibers function as suspensory ligaments of the
lens ( _L_ ). The iris ( _I_ ) is the most anterior component of the uvea and contains a central
opening, the pupil.

The outermost layer of the eyeball, the **fibrous layer**, consists of the **sclera** ( _S_ )
and the **cornea** ( _C_ ). Both of these contain collagenous fibers as their main structural
element; however, the cornea is transparent, and the sclera is opaque. The extrinsic
muscles of the eye insert into the sclera and affect the movements of the eyeball. These
are not included in the preparation, except for two small pieces of a muscle insertion
( _arrows_ ) in the _lower left_ and _top center_ of the illustration. Posteriorly, the sclera is
pierced by the emerging **optic nerve** ( _ON_ ). A deep depression in the neural retina
lateral to the optic nerve (above the _ON_ in this figure) is the fovea centralis ( _FC_ ), the
thinnest and most sensitive portion of the neural retina.


The lens is considered in Plate 24.4 (page 1016). Just posterior to the lens is the
large cavity of the eye, the **vitreous cavity** ( _V_ ), which is filled with a thick jelly-like
material, the vitreous humor or body. Anterior to the lens are two additional, fluid-filled
chambers of the eye, the **anterior chamber** ( _AC_ ) and the **posterior chamber**
( _PC_ ), separated by the iris.


**AC,** anterior chamber **C,** cornea
**CB,** ciliary body
**Ch,** choroid
**FC,** fovea centralis **I,** iris
**L,** lens
**ON,** optic nerve
**OS,** ora serrate
**PC,** posterior chamber **R,** retina
**S,** sclera
**V,** vitreous cavity
**arrows,** muscle insertions


**layer** (between the rods and cones and the intermediate neuronal layer) and the
**inner plexiform layer** (between the intermediate layer and the ganglion cells),
resulting in summation and neuronal integration. Finally, the ganglion cells send
their axons to the brain as components of the optic nerve.

##### Optic disc and nerve, eye, human, hematoxylin and eosin (H&E) ×65.


The site where the optic nerve leaves the eyeball is called the
**optic disc** ( _OD_ ). It is characteristically marked by a depression,
evident here. Receptor cells are not present at the optic disc, and
because it is not sensitive to light stimulation, it is sometimes
referred to as the _blind spot_ .
The fibers that give rise to the optic nerve originate in the retina, more specifically,
in the ganglion cell layer (see later). They traverse the sclera through a number of
openings ( _arrows_ ) to form the **optic nerve** ( _ON_ ). The region of the sclera that
contains these openings is called the **lamina cribrosa** ( _LC_ ) or cribriform plate. The
optic nerve contains a central artery and vein (not seen here) that also traverse the
lamina cribrosa. Branches of these blood vessels ( _BV_ ) supply the inner portion of the
retina.

##### Retina, eye, human, H&E ×325.


On the basis of structural features that are evident in histologic
sections, the retina is divided into 10 layers, from posterior to
anterior, as listed herein and labeled in this figure:

##### 1. Retinal pigment epithelium ( RPE ), the outermost layer of the retina 2. Layer of rods and cones ( R&C ), the photoreceptor layer of the

retina
##### 3. External limiting membrane ( ELM ), a line formed by the junctional

complexes of the photoreceptor cells
##### 4. Outer nuclear layer ( ONL ), containing nuclei of rod and cone cells 5. Outer plexiform layer ( OPL ), containing neural processes and

synapses of rod and cone cells with bipolar, amacrine, interplexiform, and
horizontal cells


##### 6. Inner nuclear layer ( INL ), containing nuclei of bipolar, horizontal,

interplexiform, amacrine, and Müller cells
##### 7. Inner plexiform layer ( IPL ), containing processes and synapses of

bipolar, horizontal, interplexiform, amacrine, and ganglion cells
##### 8. Layer of ganglion cells ( GC ), containing cell bodies and nuclei of

ganglion cells
##### 9. Nerve fiber layer ( NFL ), containing axons of ganglion cells 10. Internal limiting membrane ( ILM ), consisting of the external (basal)

lamina of Müller cells


This figure also shows the innermost layer of the choroid ( _Ch_ ), a cell-free
membrane, the lamina vitrea ( _LV_ ), also called Bruch membrane. Electron micrographs
reveal that it corresponds to the basement membrane of the pigment epithelium.
Immediately external to the lamina vitrea is the capillary layer of the choroid (lamina
choriocapillaris). These vessels supply the outer part of the retina.


**BV,** blood vessels
**Ch,** choroid
**ELM,** external limiting membrane **GC,** layer of ganglion cells **ILM,** internal

limiting membrane **INL,** inner nuclear layer (nuclei of bipolar, horizontal,
amacrine, and Müller cells) **IPL,** inner plexiform layer **LC,** lamina
cribrosa **LV,** lamina vitrea
**NFL,** nerve fiber layer **OD,** optic disc
**ON,** optic nerve
**ONL,** outer nuclear layer (nuclei of rod and cone cells) **OPL,** outer

plexiform layer **RPE,** retinal pigment epithelium **R&C,** layer of rods and
cones **arrows,** openings in sclera (lamina cribrosa)


#### **PLATE 24.3 EYE III: ANTERIOR SEGMENT**

The **anterior segment** is that part of the eye anterior to the **ora serrata**, the most
anterior extension of the neural retina, and includes the **anterior** and **posterior**


**chambers** and the structures that define them. These include the cornea and
sclera, the iris, the lens, the ciliary body, and the connections between the basal
lamina of the ciliary processes and the lens capsule (thick basal lamina of the
lens epithelium) that form the suspensory ligament of the lens, the **zonular**
**fibers** . The posterior chamber is bounded posteriorly by the anterior surface of
the lens and anteriorly by the posterior surface of the iris. The ciliary body forms
the lateral boundary. Aqueous humor flows through the pupil into the anterior
chamber, which occupies the space between the cornea and the iris, and drains
into the **canal of Schlemm** .

##### Anterior segment, eye, human, hematoxylin and eosin (H&E) ×45; inset ×75.


A portion of the **anterior segment** of the eye, shown in this
figure, includes parts of the cornea ( _C_ ), sclera ( _S_ ), iris ( _I_ ), ciliary
body ( _CB_ ), anterior chamber ( _AC_ ), posterior chamber ( _PC_ ), lens ( _L_ ),
and zonular fibers ( _ZF_ ).


The relationship of the cornea to the sclera is illustrated to
advantage here. The junction between the two ( _arrows_ ) is marked by a change in
staining, with the substance of the cornea appearing lighter than that of the sclera. The
**corneal epithelium** ( _CEp_ ) is continuous with the **conjunctival epithelium**
( _CjEp_ ) that covers the sclera. Note that the epithelium thickens considerably at the
corneoscleral junction and resembles that of the oral mucosa. The conjunctival
epithelium is separated from the dense fibrous component of the sclera by a loose
vascular connective tissue. Together, this connective tissue and the epithelium
constitute the conjunctiva ( _Cj_ ). The epithelial–connective tissue junction of the
conjunctiva is irregular; in contrast, the undersurface of the corneal epithelium presents
an even profile.

Just lateral to the junction of the cornea and sclera is the **canal of Schlemm** ( _CS_ ;
see also the next figure). This canal takes a circular route about the perimeter of the
cornea. It communicates with the anterior chamber through a loose trabecular
meshwork of tissue, the spaces of Fontana. The canal of Schlemm also communicates
with episcleral veins. By means of its communications, the canal of Schlemm provides
a route for the fluid in the anterior and posterior chambers to reach the bloodstream.


The _inset_ shows the tip of the iris. Note the heavy pigmentation on the posterior
surface of the iris, which is covered by the same double-layered epithelium as the
ciliary body and ciliary processes. In the ciliary epithelium, the outer layer is pigmented
and the inner layer is nonpigmented. In the iris, both layers of the iridial epithelium
( _IEp_ ) are heavily pigmented. A portion of the iridial constrictor muscle ( _M_ ) is seen
beneath the epithelium.

##### Anterior segment, eye, human, H&E ×90; inset ×350.


Immediately internal to the anterior margin of the sclera ( _S_ ) is the
**ciliary body** ( _CB_ ). The **iris** ( _I_ ) arises from the anterior border of
the ciliary body. The inner surface of the ciliary body forms radially
arranged, ridge-shaped elevations, the **ciliary processes** ( _CP_ ), to
which the zonular fibers ( _ZF_ ) are anchored. From the outside, the
components of the ciliary body are the ciliary muscle ( _CM_ ), the
connective tissue (vascular) layer ( _VL_ ) containing small arteries ( _A,_
_inset_ ) and veins ( _V, inset_ ) representing the choroid coat in the ciliary
body, the lamina vitrea ( _LV, inset_ ), and the ciliary epithelium ( _CiEp_, _inset_ ). The ciliary
epithelium consists of two layers ( _inset_ ), the pigmented layer ( _PE_ ) and the
nonpigmented layer ( _npE_ ). The lamina vitrea is a continuation of the same layer of the
choroid; it is the basement membrane of the pigmented ciliary epithelial cells.


The **ciliary muscle** is arranged in three patterns. The outer layer is immediately
deep into the sclera and contains the meridionally arranged fibers of Brücke. The
outermost of these fibers continues more posteriorly into the choroid and is referred to
as the _tensor muscle of the choroid_ . The middle layer is the radial group. It radiates
from the region of the sclerocorneal junction into the ciliary body. The innermost layer
of muscle cells is circularly arranged. These are seen in cross section. The circular
artery ( _CA_ ; barely discernible) and vein ( _CV_ ) for the iris, also cut in cross section, are
just anterior to the circular group of muscle cells.


**A,** artery
**AC,** anterior chamber **C,** cornea
**CA,** circular artery **CB,** ciliary body
**CEp,** corneal epithelium **CiEp,** ciliary epithelium **Cj,** conjunctiva
**CjEp,** conjunctival epithelium **CM,** ciliary muscle
**CP,** ciliary processes **CS,** canal of Schlemm **CV,** circular vein
**I,** iris
**IEp,** iridial epithelium **L,** lens
**LV,** lamina vitrea
**M,** iridial constrictor muscle **npE,** nonpigmented layer of ciliary epithelium

**PC,** posterior chamber **PE,** pigmented layer of ciliary epithelium **S,**
sclera

**V,** vein
**VL,** vascular layer (of ciliary body) **ZF,** zonular fibers
**arrows,** junction between cornea and sclera


#### **PLATE 24.4 EYE IV: SCLERA, CORNEA, AND LENS**

The transparent **cornea** is the primary dioptric (refractive element) of the eye and
is covered with nonkeratinized stratified squamous epithelium. Its stroma consists


of alternating lamellae of collagen fibrils and fibroblasts ( **keratocytes** ). The fibrils
in each lamella are extremely uniform in diameter and uniformly spaced; fibrils in
adjacent lamellae are arranged at approximately right angles to each other. This
orthogonal array of highly regular fibrils is responsible for the transparency of the
cornea. The posterior surface is covered with a single layer of low cuboidal cells,
the **corneal endothelium**, which rests on a thickened basal lamina called
**Descemet membrane** . Nearly all of the metabolic exchanges of the avascular
cornea occur across the endothelium. Damage to this layer leads to corneal
swelling and can produce temporary or permanent loss of transparency.

The **lens** is a transparent, avascular, biconvex epithelial structure suspended
by the zonular fibers. Tension on these fibers keeps the lens flattened; reduced
tension allows it to fatten or **accommodate** to bend light rays originating close to
the eye to focus them on the retina.

##### Corneoscleral junction, eye, human, hematoxylin and eosin (H&E) ×130.


This low-magnification micrograph shows the full thickness of the
sclera just lateral to the **corneoscleral junction** or limbus. To the
_left_ of the _arrow_ is sclera; to the _right_ is a small amount of corneal
tissue. The **conjunctival epithelium** ( _CjEp_ ) is irregular in thickness and rests on a
loose vascular connective tissue. Together, this epithelium and underlying connective
tissue represent the **conjunctiva** ( _Cj_ ). The white opaque appearance of the sclera is
due to the irregular dense arrangement of the collagen fibers that make up the stroma
( _S_ ). The **canal of Schlemm** ( _CS_ ) and small blood vessels ( _BV_ ) are seen at the _left_
close to the inner surface of the sclera near the border with anterior chamber ( _AC_ ) of
the eye.

##### Corneoscleral junction and canal of Schlemm, eye, human, H&E ×360.


Uppermost figure is a higher magnification micrograph showing the
transition from the corneal epithelium ( _CEp_ ) to the irregular and thicker
conjunctival epithelium ( _CjEp_ ) covering the sclera. Note that Bowman
membrane ( _B_ ), lying under the corneal epithelium, is just discernible but disappears
beneath the conjunctival epithelium. The next figure shows a higher magnification of
the canal of Schlemm ( _CS_ ) than does the _top left_ figure. That the space shown here is
not an artifact is evidenced by the endothelial lining cells ( _En_ ) that face the lumen.

##### Cornea, eye, human, H&E ×175.


This low-magnification micrograph shows the full thickness of the **cornea** ( _C_ ) and
can be compared with the sclera shown in the figure at the _left_ . The **corneal**


**epithelium** ( _CEp_ ) presents a uniform thickness, and the underlying
stroma ( _S_ ) has a more homogeneous appearance than the stroma of the
sclera (the white spaces seen here and in the figure at the _left_ are
artifacts). Nuclei ( _N_ ) of the keratocytes of the stroma lie between
lamellae. The corneal epithelium rests on a thickened anterior basement
membrane called **Bowman membrane** ( _B_ ). The posterior surface of
the cornea facing the anterior chamber ( _AC_ ) is lined by a simple squamous epithelium
called the **corneal endothelium** ( _CEn_ ); its thick posterior basement membrane is
called **Descemet membrane** ( _D_ ).

##### Corneal epithelium and endothelium, eye, human, H&E ×360.


Uppermost is a higher magnification micrograph showing the
**corneal epithelium** ( _CEp_ ) with its squamous surface cells, the very
thick homogeneous-appearing **Bowman membrane** ( _B_ ), and the
underlying stroma ( _S_ ). Note that the stromal tissue has a homogeneous appearance, a
reflection of the dense packing of its collagen fibrils. The flattened nuclei belong to the
keratocytes. Lowermost figure shows the posterior surface of the cornea. Note the thick
homogeneous **Descemet membrane** ( _D_ ) and the underlying **corneal**
**endothelium** ( _CEn_ ).

##### Lens, eye, human, H&E ×360.


This micrograph shows a portion of the lens near its equator. The
lens consists entirely of epithelial cells surrounded by a homogeneousappearing **lens capsule** ( _LC_ ) to which the zonular fibers attach. The
lens capsule is a very thick basal lamina of the epithelial cells. Simple
cuboidal lens epithelial cells are present on the anterior surface of the lens, but at the
lateral margin, they become extremely elongated and form layers that extend toward
the center of the lens. These elongated columns of epithelial cytoplasm are referred to
as **lens fibers** ( _LF_ ). New cells are produced at the margin of the lens and displace the
older cells inwardly. Eventually, the older cells lose their nuclei, as evidenced by the
deeper portion of the cornea in this micrograph.


**AC,** anterior chamber **B,** Bowman membrane
**BV,** blood vessels
**C,** cornea
**CEn,** corneal endothelium **CEp,** corneal epithelium **Cj,** conjunctiva
**CjEp,** conjunctival epithelium **CS,** canal of Schlemm **D,** Descemet

membrane **En,** endothelial lining cells **LC,** lens capsule
**LF,** lens fibers


**N,** nuclei
**S,** stroma