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EYE LECTURE

Vision is a highly developed sense in man. In the sighted, it is the dominant sense used to determine thecondition of our world. We'll begin by reviewing the parts of the eye ball that you probably learned backin 6'th grade. The transparent external surface of the eye that bulges forward is the cornea. The whites ofyour eyes, famous from the battle of Bunker Hill, are the part of a tough outer coat that surrounds all theeye except the cornea. This outer coat is called the sclera. The front of the sclera, where the whites are, iscovered by conjunctiva, an epithelial mucous membrane that is reflected around the inside surface of theeyelids forming the conjunctival sac. Inflamation of this epithelium and its underlying vessels is termedconjunctivitis. The eyelids protect both the cornea and conjunctiva. Light enters the cornea, passes throughthe anterior chamber of the eye, which is filled with aqueous humor and through the pupil, which isbordered by the free surface of the iris. Next it passes through thelens. The majority of the refraction of the light (bending of light tofocus the image on the back of the eye) is produced by the cornea,but the lens produces adjustable refraction, due to the action of themuscles in the ciliary body. The light then passes through thevitreous humor of the vitreous chamber and strikes the retina. Theretina contains the photoreceptors and other neural elements. Thelight passes through all the neural elements to activate thephotoreceptors. They in turn activate neurons within the retina,some of which send their axons out in the optic nerve to contact thecentral nervous system. The eye ball is covered by two connectivetissue coats that sustain it and maintain its shape: the choroid andthe previously mentioned sclera. Remember, there are sixextraocular muscles that attach to the sclera and direct the eye.

DevelopmentYou will recall from embryology that the retina, the part of the eyethat senses visual input, is actually an outgrowth of the brain. Earlyon in development, the optic vesicle bulges out on either side of theforebrain. It extends toward a thickened area of the surface ectodermcalled the lens placode. The optic vesicle invaginates as itapproaches the lens placode to form the optic cup. It remainsconnected with the brain by the optic stalk, which develops into theoptic nerve. The lens placode also invaginates. It separates from thesurface ectoderm to form the lens vesicle. The optic cup derivativesmake up the INNER TUNIC of the eye. This tunic has two parts:pars optica and pars caeca. Pars optica (seeing part) is the retina. Itconsists of the inner layer of the cup, which develops into the 9-layered neural retina, and the outer layer, which is the one cell thicklayer retinal pigment epithelium. Pars caeca (blind part) consists of atwo cell thick epithelium that lines the ciliary body and the posteriorsurface of the iris. The lens vesicle becomes the lens. Twoadditional layers develop out of the neural crest cells and themesenchyme surrounding the optic cup- the vascular tunic and thefibrous tunic. The vascular tunic makes up the bulk of the iris andciliary body, and it extends behind pars optica as the choroid. The

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fibrous tunic consists of two parts. Posteriorly, the sclera surrounds the other parts of the eyeball. In front,the clear cornea contains the second component of the fibrous tunic. However, the external surface of thecornea is actually of ectodermal origin. The anterior chamber develops as a cavity between themesenchyme of the iris and sclera.

Histologic Subdivisions: Eyelid & Tear filmNow lets take a closer look at the structures of the eye,working from anterior to posterior. The outermost structure isthe eyelid, which protects the eye from intense light and fromphysical threats. (see Three Stooges for details). In addition,the eye lids blink regularly to maintain the protective tearfilm. Externally the lid has thin skin with a very loosesubcutaneous layer that contains no fat. Beneath theconnective tissue is found a layer of thick bundles of striatedmuscle fibers belonging to the orbicularis oculi muscle.Distonia with over-action of the orbicularis oculi muscle iscalled blepharospasm. This muscle is supplied by the VII'thcranial nerve (facial nerve) and acts to close the eye lids.Underneath the orbicularis oculi muscle is a thick area ofdense connective tissue termed the tarsal plate that stiffensthe eyelid. It contains a large compound branched alveolargland, the tarsal gland of Meibohm. Two muscles attach tothe tarsal plate in the upper lid: the levator palpebraesuperioris and the superior tarsal muscle (Muller's). To openthe eye, these muscles pull up the tarsal plate and roll the lidup over the eyeball, like it was the door to a bread box. Only

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the inferior tarsal muscle is present in the lower lid. The levator is a striated muscle that is supplied by theIII cranial nerve (oculomotor nerve). The tarsal muscles are arranged as slips of smooth muscle fibers thatconnect the levator tendon and the trasal plate. They are supplied by the sympathetic system; i.e. thepostganglionic motor neurons lie in the superior cervical ganglion. The preganglionics lie in theintermediolateral gray column at T1&2. Both muscles operate tonically to hold the eyelids open. The backsurface of the eyelid is a mucous membrane, lined with a variable epithelium, that makes up part of theconjunctival sac. The tear film is protected from evaporation and maintained within the conjunctival sacby the oily (lipid) secretion of the tarsal gland, which empties at the mucocutaneous junction. At the frontedge of the lid are the lashes, which have an associated, specialized apocrine gland, the Glands of Moll.The lashes are levator arms that activate sensory nerves to trigger a blink reflex. Thus, at the bottom of theupper lid, the mucocutaneous junction, glands of Moll and Meibohm, lashes and orbicularis oculi musclecan be seen. At the top of the lid, both the tendon of the levator muscle and the tarsal muscle slips can beobserved attaching to the tarsal plate. These structures are all internal to the orbicularis oculi muscle.

The tear film is produced by the lacrimal gland following parasympathetic stimulation. [Postganglioniccells in the pterygopalatine ganglion, supplied by preganglionic fibers that travel in the facial nerve (C.N.VII).] This gland is entirely serous. The tear film allows dissolved oxygen to nourish the avascular cornealepithelium and it creates a smooth surface on the cornea to evenly refract the light. It also contains alysozyme with antibacterial action. Low output results in a syndrome called dry eye.

CorneaThe cornea's outer layer is a (non-cornified)stratified squamous epithelium, up to 5-6 cellsthick, called the anterior corneal epithelium.This epithelium is an ectodermal derivative.The outer cell layer of the epithelium has shortmicrovilli that help hold the tear film in place.Beneath the epithelium is an outer tunic layerof thick Type I collagen fibers and specializedfibroblasts called keratocytes. The collagenfibers in the stroma are all 35 nm in diameter,and are arranged in an extremely orderlyfashion. The layers have perpendicularorientations and the ground substance is rich inwater binding glycosaminoglycans. All this isnecessary to achieve transparency. The

outermost fibrous layer is called Bowman's layer or the anterior limiting membrane. The rest is the stromaor substantia propria of the cornea. The posterior surface of the cornea is lined by a single layer ofsquamous mesothelium, the posterior corneal epithelium. Between the posterior epithelium and thesubstantia propria is a thickened basement membrane, termed Descemet's membrane. Descemet'smembrane also shows a very orderly array of fibers, but these are Type VIII collagen fibrils arranged intoa hexagonal pattern. The posterior epithelium (which was called an endothelium in the past) is made up ofsquamous cells that are interdigitated and joined by tight junctions. These cells control the flow ofnutrients from the aqueous humor into the substantia propria. The corneal stroma is avascular. All of itsnutrients must come either from the aqueous humor or vessels along its periphery at the scleral junction.Oxygen is supplied to the anterior epithelium by the tear film, and to the rest of the cornea by the aqueousand conjunctival vessels. This avascularity allows corneas to be transplanted with relative impunity. The

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posterior corneal epithelium pumps ions and moves free water out of the stroma into the aqueous.Maintaining the cornea in a slightly dehydrated state is necessary to achieve the proper refractive index.The cornea is supplied with a large number of free nerve endings (pain fibers), as you will note if you everhave anything come in contact with it.

IrisThe iris controls the amount of light passingthrough the pupil. It consists of the followingtwo layers from the vascular tunic: Anterior Iridial border: An irregular layer offibroblasts with an underlying layer ofmelanocytes. Iris stroma: Very loose connective tissue withvessels and melanocytes.

And two layers from the inner tunic: Anterior iridial epithelium - which includesthe dilator pupillae muscle. Posterior iridial epithelium - Highlypigmented cells on the back surface of the iris.

Cells of the anterior iridial epithelium are actually made up of two parts: a modified myoepithelial processwith myofilaments, and the rest of the cell which looks like epithelium with melanin granules. It isinnervated by the sympathetic system, so its postganglionic motor neurons lie in the superior cervicalganglion. A second iris muscle that controls the pupil, the sphincter (or constrictor) pupillae muscle islocated along the pupillary margin. It derives from the same optic cup layer as the anterior irdialepithelium, but these cells separate from the inner tunic and come to look like typical smooth muscle. Thesphincter pupillae muscle has a parasympathetic innervation. The postganglionic motoneurons are in theciliary ganglion and the preganglionic fibers travel with the III’rd nerve (oculomotor nerve). The action ofthe two muscles in the iris control the size of the pupil in response to ambient light and emotional levels.The color of the iris is determined by the number of melanocytes in the stroma.

Aqueous HumorNext consider the anterior and posterior chambers. These are filled with aqueous humor. The aqueoushumor is produced by the processes of the ciliary body (pars plicata). It passes from the posterior to theanterior chamber of the eye, via the pupil, and drains out the "angle" of the eye, where the iris meets thecornea (iridocorneal angle). Aqueous humor has high levels of NaCl, bicarbonate, amino acids andascorbate, but relatively low levels of glucose and almost no protein. The ciliary body is lined by the twolayered epithelium of pars caeca of the inner tunic. The inner layer is unpigmented and the outer layer ispigmented, and so they are termed the unpigmented and pigmented ciliary epithelium, respectively. Beneath them is the stratum vasculosum of the vascular tunic. This layer of a loose connective tissuecontains fenestrated capillaries. The unpigmented ciliary epithelial layer cells have tight junctions betweenthe cells, and constitute the blood aqueous barrier that regulates the content of the aqueous humor. Theproduction rate of aqueous is defined by the blood pressure and flow in the fenestrated vessels of thestratum vasculosum. As noted above, the aqueous leaves the anterior chamber via the iridiocorneal angle. The mesothelium in this region has an unusual structure, and is called the trabecular meshwork. Theaqueous exits through the trabecular meshwork and is collected in the canal of Schlemm. The canal of

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Schlemm drains into the deep and episcleral venous plexi. There are myoid cells present in the trabecularmeshwork that act to control aqueous outflow into the canal of Schlemm. The production of aqueoushumor must be strictly matched with the drainage into the canal of Schlemm or glaucoma results. In thisdisease, pressure builds up in the aqueous and is transmitted back to the retina, where it eventually closesdown the retinal vessels causing cell death and blindness. Glaucoma is treated by changing either theproduction or outflow of the aqueous. Drugs that manipulate ciliary blood pressure or open theiridocorneal angle by constricting the pupil are often used, or, in some cases lasers may be used to openthe outflow through the angle. In the future, drugs that specifically effect the myoid cells in the trabecularmeshwork may be employed. The general region where the cornea meets the sclera is termed the limbus. Here the anterior cornealepithelium becomes the conjunctiva, with its underlying lamina propria, and the substantia propria of thecornea meets the sclera. At this junction, the collagen fibers of the sclera run parallel with the edge of thecornea (Tenon's Capsule) to maintain its bulging form. Unfortunately, you can not discern this orientationchange in your material.

Lens and Ciliary MuscleThe lens produces adjustable refraction of the image. The degree of refraction is adjusted relative to thedistance between the eye and the object. This focusing mechanism is called lens accommodation. The lensis surrounded by a thickened basal lamina- the lens capsule, which is produced by the lens cells. Theseare organized into a single layer of cuboidal cells anteriorly, the anterior lens epithelium, the posteriorcells lengthen to become the lens fibers. Cells along the equator of the lens slowly reproduce and migrateinternally, lengthening as they go. This region of younger nucleated fibers is referred to as the lens cortex. In the middle of the lens, the cells loose their nuclei and organelles to become entirely filled with atransparent, ordered array of proteins, called crystalins. This region, the lens nucleus, has the best optics,but does not accommodate (change shape) as well as the softer cortex.

The lens is held in place by a set of delicate fibers arranged like spokes of a bicycle. They are termed the

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suspensory ligament, or zonule of Zinn. The zonuleattaches into the lens capsule and it originates in the ciliarybody. The shape of the anterior surface of the lens ischanged by the action of the muscles of the ciliary bodyupon these fibers. When the ciliary muscle in the ciliarybody is relaxed, the tension in the zonule of Zinn pulls onthe edge of the lens, flattening its anterior surface andreducing the degree of refraction. This is the state whenviewing objects in the distance. To focus on objects closeup, the ciliary muscle contracts, producing a slack zonulethat, in turn, reduces the tension on the equator of the lens.The anterior surface of the lens rounds up, due to its ownelasticity, and greater refraction is achieved. This action ofthe ciliary muscle is under parasympathetic control. Thepostganglionic motor neurons are located in the ciliaryganglion and the preganglionic axons exit with the III'rdnerve, the oculomotor.

There are several disorders of vision that you should beaware of. Among them are presbyopia, hyperopia andmyopia. As noted above, as we age the nucleus, the lesspliable portion of the lens, grows. This limits our powersof accommodation. Eventually the actions of the ciliary muscle are ineffectual and the brain gives uptrying to accommodate for nearby targets. One then becomes presbyopic. In hyperopia, the eye ball iseither too short, or too little refraction is produced by the cornea (it too flat). As in presbyopia, near targetscan't be focused, and the person is said to be farsighted. By contrast, in myopia, the eyeball is either toolong or the degree of refraction produced by the cornea is too great (too curved). Distant targets are out offocus, and the person is said to be nearsighted. There is evidence that myopia may be induced by visualexperience (too much near viewing). When you look at an object close to you, 3 processes occur: theciliary muscle contracts to focus the near target, the pupil constricts due to the action of the iris sphincterto increase depth of field, and both eyes move medially (converge) due to the action of the medial rectusmuscle. This is the near triad, and the axons for all three components run through the oculomotor (III)nerve.

The ciliary body has two parts: Pars Plicata and Pars Planum. Pars plicata has been discussed as the site ofthe ciliary processes where the aqueous humor is produced. Pars planum produces part of the contents ofthe vitreous humor. Specifically, it controls the degree of hydration, and it secretes glycosaminoglycansthat hold water in the vitreous as a jell. In addition, fibroblasts are suspended within the vitreous andproduce a form of collagen. At the front of the vitreous chamber, the suspensory ligament fibers may beobserved running from between the ciliary process up to the lens. Other long fibers of the suspensoryligament run from pars planum. There are fibers in the ciliary muscle arranged to run parallel with boththese sets of suspensory ligament fibers. The posterior edge of the ciliary body, the place where pars caecastops and the multilayered pars optica begins, this border is called the ora serata.

RetinaLight, focused by the lens, passes through the vitreous humor and into the retina. It must pass throughseveral layers of cells and processes before it reaches the photoreceptors. The retina has ten layers:

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1. Inner limiting membrane 2. Nerve fiber layer 3. Ganglion cell layer 4. Inner plexiform layer 5. Inner nuclear layer 6. Outer plexiform layer7. Outer nuclear layer 8. Outer limiting membrane 9. Receptor Layer or Layer of rods and cones 10. Pigment epithelium.

The first 9 layers constitute the pars nervosa or the neural retina. Light passes from the vitreoussequentially through the first 8 layers. It is absorbed either by receptor molecules in the rod and cone layer(9), or by pigment in the pigment epithelium (10) and choroid. The pigment epithelium prevents thenon-absorbed light from being reflected back onto the receptors. Light activation of the rod and cone layerproduces a wave of nervous activity that passes back through layers 7-2. In the retinal periphery, near theora serrata, there are many fewer cells and our vision is much less precise. The most precise area of visionin man is the fovea centralis. There the photoreceptors are densest and the overlying neurons have beenpushed aside. The ganglion cell axons traveling in the fiber layer exit in the optic nerve, which piercesboth the choroid and the sclera at the blind spot. The depression at this point is called the optic papilla.The vessels that supply the retina, branches of the central retinal artery, enter here and fan out to supplythe retina. Changes in the health of the eye are often first noticeable as changes in the optic papilla.

ChoroidThe choroid has 4 ill-defined layers.

Suprachoroid: The densely pigmented layer located at the outer surface.Substantia propria: The region with the large vessels is the substantia propria (stroma) of the

choroid. Choriocapillaris: Thin capillaries located internal to the substantia propria make up the

choriocapillaris. Bruch's membrane: The basement membrane dividing the choriocapillaris from the retinal

pigment epithelium is called Bruch's membrane.

Please note the intimate relationship of the pigmentepithelium of the retina and the choroid in your slidesets. The glassy membrane where they meet is Bruch'smembrane. The layer with thin capillaries is thechoriocapillaris, and the overlying area is thesubstantia propria. You will need 100 X oil to seeBruch's membrane. The substantia propria has largervessels and copious amounts of pigment. It isgenerally not possible to define the suprachoroid as adiscrete layer, so you do NOT have to. Thechoriocapillaris is responsible for nourishing thereceptor cells and pigment epithelium. The rest of theretina (layers 1-8) is fed by branches of the centralretinal artery that enters with the optic nerve. You may

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recall from the beginning of the lecture that embryologically the nervous portion of the retina comes to lieagainst the pigment epithelium by invagination. This attachment is not that strong. Consequently, theretina may become detached in accidents. If this retinal detachment is not corrected quickly, the receptorcells die where they are no longer close enough to the choriocapillaris to be nourished. In other diseases,Bruch's membrane can become abnormally thickened, blocking the flow of nutrients to the posteriorretina.

The blood flow to the retina is actually modulated in response to light. If this modulation does not occurthere is eventual breakdown of the retinal cells. A local network of nitrous oxide (NO) producing cellsmodulates blood flow. These cells are regulated locally, and by postganglionic parasympathetic input fromthe pterygopalatine ganglion.

Sclera Officially, the sclera has 3 sublamina:

Episclera - which has vessels and adipose tissue. Substantia propria - which has thick bundles of collagen.

Lamina fusca - a more heavily pigmented layer at the junction with the choroid.However, I can't make out this last (fusca) layer so you need NOT find it in lab.

Transmission EM demonstrates the relatively irregular organization of the scleral Type I collagen fibers,in contrast with the well ordered fibers of the cornea. During pre- and postnatal development the shape ofthe eye is tightly regulated by controlling the production and organization of this collagen. Postnatally, theretina is capable of noting whether the images it receives are in focus and sends signals to the fibroblastsin the sclera to regulate their activity. This in turn controls the size of the growing eyeball. Some formsof myopia may be induced through mal-adaptation of this process. In fact, according to this "near workhypothesis", the eye grows into being myopic, if it does too much near viewing.