The+Histology+of+the+Eye

=**Objectives**=


 * 1. Identify the three tunics (major layers) of the eye and sub-components of each.**

The eye has three major layers: the tunica fibrosa, the vascular or uveal layer, and the retinal layer. The tunica fibrosa layer contains the translucent cornea anteriorly and a tough elastofibrous sclera posteriorly. The vascular layer contains the iris anteriorly, the ciliary body which suspends the lens on the zonules of zinn, and the choroid. The retinal layer contains the retinal pigment epithelium, and the neural retina which together make up the 10 layers of the retina.


 * 2. Identify the chambers of the eye, boundary structures for each, and contents of each.**

The internal aspect of the eye is divided up into three chambers: an anterior chamber, posterior chamber, and a vitreous chamber. The anterior chamber is bound abteruirkt by the endothelium of the cornea and posteriorly by the lens, iris, and ciliary body. The posterior chamber is bound anteriorly by the iris, and posteriorly by the lens and laterally by the ciliary body. Both are filled with a nutritive ultrafiltrate of plasma called Aqueous Humor which is produced by the ciliary body and flows from the posterior to the anterior chamber where it is drained into the canal of Schlemm.

The vitreous chamber is bound by the lens and the posterior wall of the eyeball. It is filled with a transparent homogeneous gelatinous intercellular substance known as the vitreous body which functions to help the eyeball hold its shape and keep the lens and retinal layers in place. The source of the vitreous body is not known but is consists of clear amorphous ground substance (GAGs) and thin randomly disposed collagen fibrils, and has a high water content (90% water). It has the consistency of soft gello and is roughly spherical expect for the depression at its anterior pole to accommodate the lens. It is adherent to the peripheral retina and the ciliary epithelium.


 * 3. Identify the layers of the cornea and cellular composition of each.**

The cornea consists of the anterior 1/6 of the tunica fibrosa and is a colorless transparent structure. The cornea is continuous with the sclera at the limbus but has more curvature, allowing it to provide 2/3 of the focusing power of the eye. It is relatively avascular and receives most of its nutrients from the aqueous humor. It has a low hydration level in order to maintain clarity. The corneal consists of five layers: epithelium, Bowman’s membrane, lamina propria, Descemet’s membrane, and the corneal endothelium.

The epithelium is the outermost layer of stratified squamous non-keratinized epithelium (5-6 layers thick) with cells connected by intracellular bridges. They are densely innervated with pain sensitive nerve fibers responsible for protective reflexes (blinking, lacrimation). The superficial cells are flat squamous cells connected by desmosomes and have microvilli on their apilca surface to maintain a film of most tears over the cornea. The basal layer of the epithelium are rapidly mitotic and can replace damaged corneal tissues (7-10 day turnover).

> The tear film is renewed after each eyeblink and has three layers itself. The superficial layer consists of an oily secretion derived from the sebaceous glands on the inner eyelid. The middle layer is watery fluid derived from the lacrimal glands, containing lysozmes and immunoglobulins. The inner layer consists of mucopolysaccharides secreted by the goblet cells of the conjunctiva.

Bowman’s membrane is a thin acellular layer composed of randomly arranged collagen fibers closely adherent to the basement membrane of the overlying epithlelial cells, serving as protection against bacterial infection.

The lamina propria is the thickest layer (90% of cornea) and consists of regularly arranged lamellae of collagen fibrils (type I), fibrocytes, and amorphous ground substance (keratin, chondroiton sulfates).

Descemet’s membrane is the thick basement membrane of the epithelial layer. It is adherent to the corneal endothelium by hemidesmosomes.

The corneal endothelium is the simple squamous inner lining of the cornea. It actively transports water through transcellular endocytosis out of the connective tissue lamina propria to maintain corneal clarity. These simple squamous cells are linked by desmosomes and occluding junctions and are responsible for secreting Descement’s membrane.

The sclera is a tough white fibrous tissue covering the posterior 5/6 of the tunica fibrosa and forms the capsule for the pack part of the eye. It is composed of three layers: the episclera, scleral stroma, and the lamina fusca.

The epsiclera is the external surface layer of dense vascularized connective tissue attached to a dense layer of connective tissue surrounding the eye called Tennon’s Capsule (See Orbit).

The scleral stroma are sheets of collagen fibers (type I) in different orientations parallel to the surface. The collagen layers are interspersed with melanocyte fibrocytes, amorphous ground substance and an network of elastic fibers. The stromal is relatively avascular with a high water content, giving it a white opaque color.

The lamina fusca is the innermost layer of the sclera and contains fine collagein fibrers which blend with the adjacent choroid layer of the eye. In the back of the eyeball,the entire sclera is continuous with the dura mater covering the optic nerve (CN II). The optic nerve pierces the sclera as it exists the eyeball at the lamina cribrosa.


 * 4. Identify the layers of the choroid region of the eye.**

The choroid layer is the vascular layer of the eye just internal to the sclera, extending posteriorly from the ciliary body across the entire posterior aspect of the eyeball. It consists of 4 layers: suprachoroid layer, vessel layer, choriocapillaris, and Bruch’s (Glassy) membrane.

The suprachoroid layer is immediately adjacent to the inner sclera and is composed of loose connective tissue with elastic fibers which anchor it to the underlying sclera.

The vessel layer is composed of connective tissue stroma with higher collagen content than the suprachoroid layer. It contains numerous choroidal arteries and choroidal veins which supply parts of the retina and sclera. It also contains numerous melanocytes which serves to absorb scattered light.

The choriocapillaris is a single layer of wide fenestrated capillaries which supply the surrouding tissues and outer 1/3 of the retinal layer.

Bruch’s membrane is formed by a network of collagen and elastic fibers sandwiched in between the basement membranes of the choriocapillaris and the retinal pigment epithelium.


 * 5. Identify the ciliary body and detail its function.**

The ciliary body is a thickening of the choroid which forms a ring around the eye on the inner aspect of the sclera just behind the iris. It is composed of loose connective tissue and smooth muscle covered by a double cuboidal epithelium consisting of a superficial non-pigmented layer and a deep pigmented layer. The cells of this double layer of cuboidal epithelium are inserted head-to-head and connected by desmosomes such that each layer has its own basement membrane. This provides a barrier function (blood-aqueous barrier) which keeps the aqueous humor produced by the ciliary body separated from the rest of the body.

The ciliary body has two functions:

(1) vessels in the ciliary body are the source of aqueous humor of the anterior and posterior chambers of the eye. Aqueous humor is filtered out of the blood vessel into the posterior chamber by the capillaries of the ciliary processes and is the chief source of nutrients for the avascular lens and cornea. The aqueous humor is transported out of the interior ciliary body by the pigmented epithelial cells of the ciliary body whose basement membrane provides a blood-aqueous barrier.

(2) the ciliary body regulates the shape of the lens by action of the ciliary muscles to accommodate the eye for close and distant vision. These muscles are controlled by the parasympathetic nervous system and are attached circumferentially around the eye. Contraction of the ciliary muscles results in release of tension on the attached zonules of zinn and allows the lens to round up for close vision.

For accommodation to near visual objects, the parasympathetic nervous system causes the ciliary muscles to contract, releasing tension on the zonules of zinn, allowing the lens to increase its focusing power by increasing its curvature. For distance vision, the ciliary body is relaxed, causing the lens and the zonules of zinn to be stretched by the natural tension of the elastic choroid.


 * 6. Identify the components of the iris and pupil and relate their structure to their function.**

The iris is a disk-shaped diaphragm situated between the anterior and posterior chambers of the eye. It is divided into 4 layers: anterior limiting layer, stroma, muscular layer, and posterior epithelium.

The anterior limiting layer is a discontinuous layer of stromal cells consisting of stellate shaped fibroblasts and melanocytes. The stroma is a vascularized loose connective tissue containing melanocytes and fibroblasts. The muscular layer are two bands of smooth muscle embedded in the stroma of the iris: sphincter pupillae and dilator pupillae. The sphincter pupillae is a distinct circular band of smooth muscle at the margins of the pupil that close down the pupil when contracted under parasympathetic nervous stimulation. The dilator pupillae is a radially oriented myoepithelial smooth muscle near the posterior border of the iris that dilates the pupil when contracted under sympathetic nervous stimulation. The posterior epithelium is a simple cuboilda pigmented epithelium that is continuous with the pigmented epithelium of the retina.

The iris adjusts the pupil aperture to alter the amount of light that enters the eye, permitting vision under a wide variety of light intensities.

The epithelial cells of the iris are heavily pigmented with melanin to prevent light from entering the eye anywhere other than the pupil and to reduce light scattering in the interior of the eye. Eye color results from varying amounts of melanin in the stroma of the iris against the heavily pigmented cells in the posterior epithelium. That is, everybody has pigment on the posterior epithelium, but people vary in the amount of pigment in the stroma. Reduced melanin the stroma results in blue eyes; increased melanin in the stroma produced brown eyes.


 * 7. Identify the canal of Schlemm (scleral venous sinus), its function and its importance in clinical disease of the eye.**

Aqueous humor produced by the ciliary body flows through the posterior chamber into the anterior chamber and is drained from the anterior chamber by passing through a network of fibrous channels in the lateral aspect of the ciliary body called the microtrebecular meshwork. This sieve-like meshwork acts to filter out corneal waste and empties the aqueous humor into the annular canal of Schlemm located near the attachemtn of the ciliary body to the sclera in the anterior chamber.

This canal is lined with simple squamous epithelium and runs circularly around the cornea in the connective tissue of the sclera. From the canal, aqueous veins carry the fluid to the conjunctiva where it is drained into the venous blood.

The canal of Schlemm maintains a constant aqueous humor production and drainage to maintain constant intraocular pressure. If a blockage occurs, it can results in increased intraocular pressure (glaucoma) and decreased blood flow and ischemia of the retina, causing eventual blindness.


 * 8. Identify the lens of the eye and the zonules of Zinn (suspensory ligament of the lens).**

The lens is a biconvex transparent disk suspended just behind the pupil, and touching the iris. The anterior surface has an acellular elastic capsule which is rich in type IV collagen and proteoglycans associated with the simple cuboidal basement membrane just beneath the capsule.

The lens is avacuslar and contains no connective tissue; it is composed entirely of modified epithelial cells. The epithelial cells form a germinal zone at the equatorial rim of the biconvex surfaces of the lens and continue to divide throughout life, adding to the margins of the lens. Deep to the epithelium, lens cells lose their nucleus and intracellular organelles as they elongate into transparent structures called lens fibers in the direction if incoming light.. These lens fibers make up the body of the lens and is packed with transparent proteins called crystallins. The lateral borders of these fibers are connected by knob-and-socket depressions with tight junctions and gap junctions. Fibers at the center of the lens persist throughout life and are not replaced.

The inner edge of the ciliary body terminates in a series of slender ridges called ciliary processes that are attached to the suspensory ligaments of the lens by the zonules of zinn. The outer edge of the ciliary body is anchored to the choroid layer from which is emerges. The zonules of zinn are composed of microfibrils similar to elastic tissue and are attached to the equator of the lens and the ciliary body.

The lens provides 1/3 of the focusing power of the eye by changing its shape. It is soft and will round up into a lens of greater power if left alone. At rest, the lens is stretched into a flatter shape of less power by the zonules of zinn and ciliary muscles. With age, the lens fibers harden and the lens loses its ability to change shape, causing presbyopia, and resulting int eh need of reading glasses or bifocals. The lens may also become semiopaque with age, resulting in cataracts and blurred vision.


 * 9. Describe the production, flow pathway, and absorption of the aqueous humor.**

Aqueous humor is produced by the ciliary body and flows from the posterior chamber to the anterior chamber. It is drained through the microtrebecular meshwork into the canal of Schlemm located near the attachment of the ciliary body to the sclera. From the canal of Schlemm, it is drained into the aqueous veins which carry the fluid to the conjunctiva to be released into venous blood.


 * 10. Identify the retina and its ten layers.**

(1) Retinal Pigment Epithelium (RPE) > A single layer of cuboidal-columnar cells between the retina and the choroid in the posterior portion of the eye and extends over the ciliary body and the posterior iris. Functionally, this layer is related to both the choroid and the retina. It resembles a simple cuboidal epithelium of the choroid but it has no free surface under the retina, but is instead attached to Bruch’s membrane of the chorid. The apical surface of these cells have microvilli and cylindrical cytoplasmic sheaths that enclose the ends of the retinal photoreceptors to nourish the outer portions of the rods and cones and phagocytose pieces of their outer segments which are continuously shed off.

> The epithelial basement membrane and well developed tight junctions between the cells of the RPE provide a blood-retinal barrier that prevents materials from passing through to the rods and cones unless actively transported. The RPE cells contain melanin granules that, along with choroid pigment, prevent light from scattering in the back of the eyeball. There is no firm attachment between the RPE and the underlying photoreceptor layer, so the retina can detach following head trauma, causing slow death in photoreceptors unless surgically reattached.

(2) Photoreceptor Layer > The photoreceptor layer is populated by photoreceptor cells specialized for tranducing light energy into nerve impulses. There are two types of photoreptors: rods and cones.

(3) External Limiting Membrane > The photoreceptors are surrouned by Muller cells which are supportive cells analogous to glial cells. The external limiting membrane is not really a membrane and is composed of zonula adherens junctions between the cylindrical cytoplasmic rpocesses of the Muller cells and the photoreceptors.

(4) Outer Nuclear Layer > The outer nuclear layer is the region where the nuclei of the photoreceptor cells reside. The nuclei are at different distances from the external limiting membrane, giving the layer the appearance of the thick stratified epithelium.

(5) Outer Plexiform Layer > The outer plexiform layer contains basal synaptic processes of the photoreceptors as they make contact with the dendrites of two types of 2nd order cells: the bipolar cells and the horizontal cells. This region is relatively unstained in light microscopy because there are no cell bodies.

(6) Inner Nuclear Layer > The inner nuclear layer is where the cell bodies of the bipolar, horizontal and amacrine cells reside. The cells are responsible for the processing of visual signals from the photoreceptors within the retina.

(7) Inner Plexiform Layer > The inner plexiform layer is a relatively clear region where the processes of bipolar, amacrine, and ganglion cells interact synaptically to process visual information. This region also has no cell bodies like the outer plexiform layer.

(8) Ganglion Cell Layer > The ganglion cell layer contains the cell bodies of the retinal ganglion cells. This layer is variable in thickness. The retinal ganglion cells are the output neurons of the retina and support a long axon that leaves the retina as the optic nerve (CN II) to synapse in the CNS. The retinal ganglion cells are much larger than other neurons of the retina.

(9) Retinal Axon Layer > The retinal axon layer is a region where the unmyelinated ganglion cell axons travel towards the optic disk where they exit the eyball. After they leave the eyeball, they become myelinated to form the optic nerve, which is larger in diameter than the optic disk.

(10) Internal Limiting Membrane > The internal limiting membrane is not a true membrane but the basement membrane of the supportive Muller cells. Muller cells span all the layers of the retina and their cell bodies lie in one of the cellular regions and cannot be distinguished from the neurons.


 * 11. Identify the photoreceptors of the eye.**

The photoreceptors of the eye reside in the photoreceptor layer (Layer 2) though the outer plexiform layer (Layer 5) and consists of rods and cones. The distribution of photoreceptors is not random. The center of the retina near the optic nerve (CN II) has a slight depression called the fovea centralis which is especially dense in cones, which give the best visual acuity. This area is devoid of blood vessels and the remaining retinal layers are exceptionally thin here, to allow light to gain easier access to the cones. Generally, cones predominated in the central retina while rods predominate in the peripheral retina. Light striking the outer segments of the rods and cones results in hyperpolarization via a cGMP and Ca2+ dependent modulation of Na+ channels in the photoreceptor membrane.

The photoreceptor cells are subdivided into 6 parts: the outer segment, cilium, inner segment, outer fiber, cell body, and inner fiber.

The outer segment contains the broad and tapered cones and the narrow and straight rods. The outer segments of photoreceptors are composed of dense vertical stacks of membrane bound disks which arise from the repeated infolding of the apical surface of the cell membrane. This is the light sensitive region of the photoreceptors and is constantly being turned over with the ends sloughing off to be phagocytosed by the RPE cells. The disks of the photoreceptor outer segments contain vitamin A-derived photopigments composed of retinene and opsin. Rods contain rhodopsin while cones contain three varieties of photopsin (lodopsin). The rod pigment is sensitive to dim light (scotopic vision) and support night vision. The cone pigments are sensitive to bright red, green, or blue light (photopic vision) and support daylight color vision.

The cilium is a thin slender region just below the outer segment. It is unlike other cilia because it is immotile and lacks the central pair of microtubules though it contains the nine peripheral microtubule doublets. The cilium connects the outer segment to the adjacent inner segment, isolating the metabolic region from the photosensitive portion. Photoreceptor disks are thought to arise from a specialization of the cilium. That is, the cilium is the disk factory for the outer segment.

The inner segment is a slightly thicker ellipsoid region of the cell containing most of the intracellular organelles except the nucleus. The membrane of this region contains numerous K+ channels which are active in the phototransduction process. This region functions as the primary metabolic region of the photoreceptors.

The outer fiber connects the inner segment to the cell body. This thin process is surrounded by the processes of the apical surfaces of adjacent surrounding Muller cells. Muller cell processes are connected by tight junctions in this region, giving the thickened appearance of the external limiting membrane (3rd layer of the retina). The outer fiber is much less prominent in cones than in rods.

The cell body is the region of the photoreceptor that is almost entirely filled by the nucleus.

The inner fiber extends from the cell body of the photoreceptor and terminates in a specialized expanded region which forms the synaptic contact with the underyling bipolar cells. In rods, this specialized expanded presynatic region is called the spherule. In cones, it is called the pedicule. It contains numerous synaptic vesicles.