EYE

The eye can self-focus, adjust for light intensity, and convert light into electrical impulses interpreted by the brain. In humans, the eye is recessed in a bony orbit and is connected to the brain by the optic nerve. The eyeball protects and facilitates the function of the photoreceptive retina, the inner layer of the eyeball.

The eyeball consists of three tunics or layers which, from outside to inside, are (1) the sclera and the cornea, (2) the uvea, and (3) the retina (Figure 9-1).

Figure 9-1 Anatomy of the eye

Three distinct and interconnected chambers are found inside the eyeball: the anterior chamber, the posterior chamber, and the vitreous cavity (see Box 9-A). Aqueous humor circulates from the posterior to the anterior chamber. The lens is placed in front of the vitreous cavity, which contains vitreous humor. The bony orbit, the eyelids, the conjunctiva, and the lacrimal apparatus protect the eyeball.

The ophthalmic artery, a branch of the internal carotid artery, provides nutrients to the eye and the contents of the orbit. The superior and inferior orbital veins are the principal venous drainage of the eye. The veins empty into the intracranial cavernous sinus.

DEVELOPMENT OF THE EYE

A brief summary of the development of the eye is essential to the understanding of the relationship of the various layers in the eyeball. The components of the eye derive from (1) the surface ectoderm of the head; (2) the lateral neuroectodermal walls of the embryonic brain in the diencephalon region; and (3) the mesenchyme.

Lateral outpocketings of the right and left sides of the diencephalon give rise to two neuroepithelial optic vesicles, each remaining attached to the brain wall by a hollow optic stalk (Figure 9-2). The surface ectoderm of the head invaginates into the optical vesicle forming a lens vesicle that pinches off. Mesenchyme surrounds both the lens vesicle and the adjacent optic vesicle.

Figure 9-2 Development of the eye

The optic vesicle invaginates and becomes a double-walled optic cup (see Figure 9-2). The optic fissure forms when the outer layer of the optic cup becomes the pigmented epithelium. Cells in the inner layer proliferate and stratify to form the neural retina. The mesenchyme extending into the invagination of the optic cup acquires a gelatinous consistency and becomes the vitreous component of the eye. The lens vesicle is kept in place by the free margins of the optic cup and the surrounding mesenchyme.

At the outer surface of the optic cup, the mesenchymal shell differentiates into the vascular choroid coat of the eye and the fibrous components of the sclera and cornea (Figure 9-3; see Box 9-B). Posterior to the lens, the vascular choroid coat forms the ciliary body, ciliary muscle, and ciliary processes. Anterior to the lens, the choroid coat forms the stroma of the iris. The ciliary processes secrete the aqueous humor that accumulates first in the posterior chamber (between the iris and lens) and then passes into the anterior chamber (between the lens and cornea) across the pupil. The aqueous humor leaves the anterior chamber by entering into the canal of Schlemm, a small vein (sinus venosus of the sclera) encircling the eye at the anterior edge of the choroid coat.

Figure 9-3 Development of the eye

Around the rim of the optic cup, the inner and outer layers form the posterior epithelium of the ciliary body and iris. The sphincter and dilator pupillae muscles develop from the posterior epithelium.

The inner layer of the optic cup becomes the neural layer of the retina, which differentiates into photosensory cells, bipolar neurons, and ganglionic neurons (including interconnecting horizontal and amacrine cells and glial Müller cells). Axons from the ganglionic neurons form the nerve fiber layer of the retina, which converges on the optic stalk occupying the optic fissure as the optic nerve. The optic fissure becomes the escape route from the optic cup (except at its rim).

OUTER TUNIC: SCLERA AND CORNEA

The sclera (Figure 9-4) is a 1.0- to 0.4-mm-thick layer of collagen and elastic fibers produced by fibroblasts. The inner side of the sclera faces the choroid, from which it is separated by a layer of loose connective tissue and an elastic tissue network known as the suprachoroid lamina. Tendons of the six extrinsic muscles of the eye are attached to the outer surface of the sclera.

Figure 9-4 Three tunics of the eye

Cornea

The cornea is 0.8-1.1 mm thick and has a smaller radius of curvature than the sclera. It is transparent, lacks blood vessels, and is extremely rich in nerve endings. The anterior surface of the cornea is always kept wet with a film of tears retained by microvilli of the apical epithelial cells. The cornea is one of the few organs that can be transplanted without a risk of being rejected by the host’s immune system. This success can be attributed to the lack of corneal blood and lymphatic vessels.

The cornea is composed of five layers (Figure 9-5):

1. The corneal epithelium.

2. The layer or membrane of Bowman.

3. The stroma or substantia propria.

4. The membrane of Descemet.

5. The corneal endothelium.

Figure 9-5 Cornea

The corneal epithelium is stratified squamous and consists of five to seven layers of cells. Cells of the outer surface have microvilli and all cells are connected to one another by desmosomes. The cytoplasm contains cytokeratin associated with desmosomes. The epithelium of the cornea is very sensitive, contains a large number of free nerve endings, and has a remarkable wound healing capacity. At the limbus, the corneoscleral junction, the corneal epithelium is continuous with that of the conjunctiva.

Bowman’s layer is 6 to 9 μm thick, consists of type I collagen fibrils, and lacks elastic fibers. This layer is transparent and does not have regenerative capacity. Bowman’s layer is the anteriormost part of the corneal stroma, although differently organized. For this reason, it is designated “layer” instead of “membrane.” Bowman’s layer represents a protective barrier to trauma and bacterial invasion.

The highly transparent stroma or substantia propria represents about 90% of the thickness of the cornea. Bundles of types I and V collagen form thin layers regularly arranged in successive planes crossing at various angles and forming a lattice that is highly resistant to deformations and trauma. Fibers and layers are separated by an extracellular matrix rich in proteoglycans containing chondroitin and keratan sulfate.

Nerves in transit to the corneal epithelium are found in the corneal stroma.

Descemet’s membrane, one of the thickest basement membranes in the body (5 to 10 μm thick), is produced by the corneal endothelium and contains type VII collagen, which forms a hexagonal array of fibers.

The corneal endothelium lines the posterior surface of Descemet’s membrane and faces the anterior chamber of the eye. It consists of a single layer of squamous epithelial cells, with impermeable intercellular spaces preventing influx of aqueous humor into the corneal stroma. The structural and functional integrity of the corneal endothelium is vital to the maintenance of corneal transparency (see Box 9-C).

Box 9-C Corneal transplantation

• Corneal transplantation, also known as penetrating keratoplasty, is the most common form of tissue allotransplantation (Greek allos, other) with a success rate of over 90%.

• This success is related to various aspects of the cornea and the ocular microenvironment: (1) The expression of major histocompatibility complex (MHC) class II is negligible or absent in the normal cornea. (2) The cornea secretes immunosuppressive factors that inhibit T cell and complement activation (see Chapter 10, Immune-Lymphatic System). (3) Cells in the cornea express Fas ligand, which protects the eye from cell-mediated damage by eliminating apoptosis cells that can determine inflammatory damage (see Apoptosis in Chapter 3, Cell Signaling). (4) Corneal Langerhans cells (see Chapter 11, Integumentary System) and antigen-presenting cells are rare in the cornea. (5) The cornea is avascular and lacks lymphatics, thus preventing the arrival of immune elements.

MIDDLE TUNIC: UVEA

The uvea forms the pigmented vascularized tunic of the eye and is divided into three regions: (1) the choroid, (2) the ciliary body, and (3) the iris (see Figure 9-7) (see Box 9-D).

Figure 9-6 Structure of the choroid

Figure 9-7 Ciliary body

The choroid consists of three layers (Figure 9-6):

The ciliary body (Figure 9-7) is anterior to the ora serrata and represents the ventral projection of both the choroid and the retina. It is made up of two components: (1) the uveal portion and (2) the neuroepithelial portion.

The uveal portion of the ciliary body includes:

The neuroepithelial portion contributes the two layers of the ciliary epithelium:

Particular features of these two pigmented and nonpigmented epithelial cell layers are:

Figure 9-8 Structure of the ciliary epithelium and secretion of aqueous humor

The iris is a continuation of the ciliary body and is located in front of the lens. At this position, it forms a gate for the flow of aqueous humor between the anterior and posterior chambers of the eye and also controls the amount of light entering the eye.

The iris has two components: (1) the anterior uveal or stromal face and (2) the posterior neuroepithelial surface.

The anterior (outer) uveal face is of mesenchymal origin and has an irregular surface. It is formed by fibroblasts and pigmented melanocytes embedded in an extracellular matrix. The number of pigmented melanocytes determines the color of the iris. In albinos, the iris appears pink due to the abundant blood vessels. Blood vessels of the iris have a radial distribution and can adjust to changes in length in parallel to variations in the diameter of the pupil.

The posterior (inner) neuroepithelial surface consists of two layers of pigmented epithelium. The outer layer, a continuation of the pigmented layer of the ciliary epithelium, consists of myoepithelial cells that become the dilator pupillae muscle. The smooth muscle of the sphincter pupillae is located in the iris stroma around the pupil.

Three chambers of the eye

The eye contains three chambers (see Figure 9-1): (1) the anterior chamber, (2) the posterior chamber, and (3) the vitreous cavity. The vitreous is the largest component of the eye. The longest part of the optical path from the cornea to the retina is through the vitreous.

The anterior chamber occupies the space between the corneal endothelium (anterior boundary) and the anterior surface of the iris, the pupillary portion of the lens, and the base of the ciliary body (posterior boundary). The circumferential angle of the anterior chamber is occupied by the trabecular meshwork, a drainage site for the aqueous humor into the canal of Schlemm (Figures 9-9 and 9-10).

Figure 9-9 Path of aqueous humor

Figure 9-10 Canal of Schlemm

The posterior chamber (see Figure 9-9) is limited anteriorly by the posterior surface of the iris and posteriorly by the lens and the zonular fibers (suspensory ligaments of the lens). The circumferential angle is occupied by the ciliary processes, the site of aqueous humor production.

The vitreous cavity is occupied by a transparent gel substance–the vitreous humor—and extends from the lens to the retina. The vitreous humor contains mostly water (99%), hyaluronic acid, and type II collagen fibrils, a close relative of the collagen in cartilage. Recall from the discussion on the extracellular matrix of connective tissue that the glycosaminoglycan hyaluronic acid has significant affinity for water. Fully hydrated hyaluronic acid, associated with widely spaced collagen fibrils, is responsible for changes in vitreous volume. Hyaluronic acid and type II collagen are produced by hyalocytes.

LENS

The cornea, the three chambers of the eye, and the lens are three transparent structures through which light must pass to reach the retina. Note that the refractive surface of the cornea is an interface between air and tissue and that the lens is in a fluid environment whose refractive index is higher than that of air.

The lens is a transparent, biconvex, elastic, and avascular structure (Figure 9-11). Zonular fibers, consisting of elastin fibrils and a polysaccharide matrix, extend from the ciliary epithelium and insert at the equatorial portion of the capsule. They maintain the lens in place and, during accommodation, change the shape and optical power of the lens in response to forces exerted by the ciliary muscle. The zonular fibers support the lens “as guy wires support a tent.”

Figure 9-11 Lens

The lens consists of a series of concentric shells or layers forming the lens substance. The inner part of the lens is the nucleus. The outer part is the cortex. The anterior epithelium has a single layer of epithelial cells and is the source of new cells of the lens. The posterior epithelium disappears early in the formation of the lens. The anterior epithelium and lens substance are enclosed by the lens capsule. There is no epithelial cell layer under the posterior surface of the capsule.

The lens capsule is a thick flexible acellular and transparent basement membrane—like structure containing type IV collagen fibrils and a glycosaminoglycan matrix. Beneath the anterior portion of the capsule is a single layer of cuboidal epithelial cells that extend posteriorly up to the equatorial region. In the cortical region of the lens, elongated and concentrically arranged cells (called cortical lens fibers) arise from the anterior epithelium at the equator region. Cortical lens fibers contain a nucleus and organelles. The nucleus and organelles eventually disappear when the cortical lens fibers approach the center of the lens—the nuclear lens fiber region.

Lens cell differentiation consists of the appearance of unique cytoskeletal proteins: (1) filensin, an intermediate filament that contains attachment sites for crystallins and (2) lens-specific proteins called crystallins (α, β, and γ). Filensin and crystallins maintain the conformation and transparency of the lens fiber cell.

Lens cell fibers interdigitate at the medial suture region. At these contact sites, gap junctions and some spot desmosomes interlock the opposing cytoplasmic processes. The inner cortical region and the core of the lens consist of older lens fibers lacking nuclei. About 80% of its available glucose is metabolized by the lens.

Accommodation

The sharpness of distant and close images focused on the retina depends on the shape of the lens (Figure 9-12). Accommodation defines the process by which the lens becomes rounder to focus the image of a nearby object on the retina and flattens when the image of a distant object is focused on the retina.

Figure 9-12 Accommodation

Accommodation determines that the distance between the center of the lens and the retina is equivalent to the focal distance needed for the formation of a sharp image on the retina.

Three components contribute to the accommodation process: (1) the ciliary muscle, (2) the ciliary body, and (3) the suspensory ligaments, inserted at the equatorial region of the lens capsule.

When the ciliary muscle contracts, the ciliary body moves toward the lens. Consequently, the tension of the suspensory ligaments is reduced, and the elastic capsule of the lens enables the lens to acquire a spherical shape. A rounded lens facilitates close vision.

When the ciliary muscle relaxes, the ciliary body keeps the tension of the suspensory ligaments that pull at the circumference of the lens. Thus, the lens remains flat to enable distant vision. This condition is known as emmetropia (Greek emmetros, in proper measure; opia, pertaining to the eye), or normal vision.

If the eyeball is too deep or the curvature of the lens is not flat enough, the image of a distant object forms in a plane in front of the retina. Distant objects are blurry because they are out of focus, but vision at close range is normal. This condition is called myopia (Greek myein, to shut), or nearsightedness.

If the eyeball is too shallow and the curvature of the lens is too flat, the distant image is formed at a plane behind the retina. Distant objects are well resolved but objects at a closer range are not. This condition is called hyperopia (Greek hyper, above), or farsightedness.

Older people become farsighted as the lens loses elasticity. This form of hyperopia is known as presbyopia (Greek presbys, old man).

Accommodation difficulties can be improved by the use of lenses. A diverging lens corrects myopia; a converging lens corrects hyperopia.

INNER LAYER: RETINA

The retina consists of two regions (Figure 9-13): (1) the outer nonsensory retinal pigmented epithelium, and (2) the inner sensory retina (see Box 9-E).

Figure 9-13 Regions of the retina

The nonsensory retinal pigmented epithelium is a single layer of cuboidal cells extending from the edge of the optic disk to the ora serrata, where it continues as the pigmented layer of the ciliary epithelium.

The apical domain of the cuboidal nonsensory pigmented epithelium is sealed by tight junctions to form the external retinal barrier (Figure 9-14). Granules of melanin are present in the apical cytoplasm and apical cell processes. Melanin granules absorb excess light reaching the photoreceptors.

Figure 9-14 Layers of the retina

The apical surface contains microvilli that surround the outer segments of the photoreceptors (cones and rods). At this location, the sensory retina and the pigmented epithelium are attached to each other through an amorphous extracellular material, the interphotoreceptor matrix (Figure 9-15).