Intraocular Pressure Maintains the Shape of the Eye

Cameras have rigid bodies, designed to keep the film in a stable position relative to the lens. In contrast, the shape of the eye (and position of the retina) is maintained in much the same way as inflating a soccer ball maintains its shape. The collagenous sclera and cornea correspond to the wall of the soccer ball, and intraocular fluid pressure replaces air pressure. The pressure is generated by a now familiar process of fluid production, circulation, and reabsorption (Fig. 17-3). The ciliary body functions as a small outpost of choroid plexus, secreting aqueous humor across the ciliary epithelium and into the posterior chamber, the space between the iris and the lens. Pushed along by hydrostatic pressure, the aqueous humor passes through the pupil and into the anterior chamber, filters through the collagenous trabecular meshwork (analogous to arachnoid granulations) at the iridocorneal angle, and enters an endothelium-lined scleral venous sinus (the canal of Schlemm), which communicates directly with the venous drainage of the eye. The production rate (about 2 μL/min) is sufficient to completely replace the aqueous humor about 15 times a day. The space behind the lens, constituting most of the intraocular volume, is filled with gelatinous vitreous (Latin for “glassy”) humor, so the resistance to aqueous outflow afforded by the trabecular meshwork and the wall of the scleral venous sinus causes a pressure of about 15 mm Hg that is transmitted throughout the eye, maintaining its shape.

Figure 17-3 Production and circulation of aqueous humor. Components filtered through fenestrated ciliary capillaries are transported across the ciliary epithelium, enter the posterior chamber (*), move through the pupil into the anterior chamber, pass through the trabecular meshwork, and enter the scleral venous sinus. The inset is a scanning electron micrograph showing the zonular suspension of a monkey’s lens; the view is as though you were in the vitreous space, looking diagonally outward toward the back of the lens. CB, ciliary body; CP, ciliary processes (the corrugated surface of the ciliary body, bulging between zonular fibers); I, iris; L, lens; S, sclera; SC, scleral venous sinus (Schlemm’s canal); Z, zonules.

(Inset, from Rohen JW: Invest Ophthalmol 18:133, 1979.)

In much the same way that blocking the circulation or reabsorption of cerebrospinal fluid causes increased intracranial pressure, headache, and neural damage, processes that interfere with the circulation or reabsorption of aqueous humor cause the painful condition of glaucoma and, ultimately, retinal damage (see Fig. 17-14F and G).

The Cornea and Lens Focus Images on the Retina

Focusing an image requires refraction of light across one or more interfaces where there is a change in refractive index. The aqueous and vitreous humors have a refractive index only slightly lower than that of the lens, so the lens accounts for only about a third of the refractive power of the eye; its major role is adjusting the focus of the eye for near and far objects, as described later. Hence for nonaquatic vertebrates like us, most of the refraction occurs at the air-water interface at the front surface of the cornea;^* its curved shape, maintained by intraocular pressure, accounts for our ability to see 90 degrees or more to the side (see Fig. 17-32).

Figure 17-32 Normal visual field of the left eye (A), the right eye (B), and both eyes superimposed (C). The blind spot of each eye is indicated in a darker color in A and B. The view is the patient’s view of the charts on which the fields are being recorded.

One can imagine a variety of strategies for changing the focus of an optical device to accommodate to near objects—moving the photosensitive surface, moving the refractive elements, or changing the shape of the refractive elements. Different animals have adapted each of these strategies. Conventional cameras are adjusted for near or far objects by moving their lenses closer to or farther from the film; similarly, fish and most amphibians have intraocular muscles that move the lens back and forth. Arthropods cannot move or deform lenses that are part of the exoskeleton, but some have muscles that move the retina closer to or farther from the lens. Some animals have muscles attached to the cornea that can change its curvature. Terrestrial vertebrates use intraocular muscles to change the shape of the lens. Our lens is suspended by strands of connective tissue called zonules (Fig. 17-3, inset), attached at one end to the lens and at the other end to the ciliary body. At rest, the tension of this zonular suspension keeps the lens slightly flattened and the eye focused on distant objects. The ciliary muscle has some fibers oriented circumferentially that act as a kind of sphincter; contraction of these fibers pulls the ciliary attachment points of the zonules toward the center of the pupil and relaxes some of the tension in the zonular suspension. Other ciliary muscle fibers are oriented parallel to the surface of the eye; contraction of these pulls the ciliary attachment points partly anteriorly and partly toward the center of the pupil, again relaxing some of the tension in the zonular suspension. Hence, somewhat counterintuitively, contraction of the ciliary muscle allows the lens to fatten as the eye accommodates to near objects: the posterior surface of the lens is embedded in the vitreous humor and does not move much, but the anterior surface bulges out slightly.

The Iris Affects the Brightness and Quality of the Image Focused on the Retina

The range of light intensities over which we have useful vision, from starlight to bright sunlight, is an astonishing 10¹² or so—a million million-fold. This is a much greater range of intensities than receptor potentials and frequencies of action potentials can encode directly, so there are mechanisms for adapting visual sensitivity to the ambient illumination. Most of these mechanisms depend on the physiology and wiring of retinal neurons, but in addition, the iris plays a role in regulating the amount of light reaching the retina. The two posterior epithelial layers are densely pigmented, and in brown-eyed individuals the stroma contains substantial additional pigment, so essentially all light reaching the retina must first pass through the pupil, the aperture in the middle of the iris.

The size of the pupil is controlled by two smooth muscles in the iris (Fig. 17-2); both are highly unusual, in that they are derived from the same layers of neural ectoderm that give rise to the retina. The circumferentially arranged pupillary sphincter encircles the pupil at what was, embryologically, the edge of the optic cup.^* The pupillary dilator, whose fibers are arranged like spokes radiating from the sphincter, is located at the interface between the pigment epithelial layers and the stroma. The sphincter is the stronger of the two, and reflex connections mediated by the optic and oculomotor nerves constrict the pupil in response to increased levels of illumination (see Fig. 17-39). The pupillary sphincter can contract by about 80%, much more than other muscles and enough to vary the diameter of the pupil from about 8 mm to 1.5 mm. However, this corresponds to only about a thirtyfold change in area, consistent with the idea that retinal mechanisms play the major role in adjusting visual sensitivity.^†

Figure 17-39 A, Pathway of the pupillary light reflex. B and C, Pupillary consequences of damage to one optic nerve or one oculomotor nerve, respectively. In each, the upper images show the relative sizes of pupils in the dark, and the middle and lower images show the expected responses to illumination of the left and right eyes, respectively. Note that when switching illumination from the left eye to the right eye in B, the right pupil dilates in a seemingly paradoxical fashion. This is the basis of the swinging flashlight test. (The right pupil in C is always dilated, and moving the illumination to the right eye causes no change.) CN III, oculomotor nerve; EW, Edinger-Westphal nucleus; LGN, lateral geniculate nucleus.

(A, modified from Nolte J: Elsevier’s integrated neuroscience, Philadelphia, 2007, Mosby Elsevier.)

In addition to decreasing the amount of light reaching the retina, a smaller pupil improves the optical performance of the eye (just as, within limits, a smaller aperture improves the optical performance of a camera lens). This is particularly important when focusing on near objects (see Figs. 17-40 and 17-41).

Figure 17-40 Effect of pupil size on depth of focus. A, When the eye is focused on objects at distance X and the pupil is large, the image of a point at distance Y will be out of focus and smeared out over a relatively large area. B, A smaller pupil results in a smaller blur circle for a point at distance Y; objects over a greater range of distances are now in acceptable focus.

Figure 17-41 Pathway of the near reflex. Although the efferent projections from visual association cortex to the oculomotor nucleus are indicated as arising in the occipital lobe, the exact site of origin is not known with certainty. CG, ciliary ganglion; CN III, oculomotor nerve; LGN, lateral geniculate nucleus; Oc, oculomotor nucleus.

(Modified from Nolte J: Elsevier’s integrated neuroscience, Philadelphia, 2007, Mosby Elsevier.)

A System of Barriers Partially Separates the Retina from the Rest of the Body

A further indication of the origin of the retina from the neural tube is a blood-retina barrier system, parallel to the three-part barrier system in and around the brain (see Fig. 6-27), that separates the neural retina from other parts of the body. The endothelial cells of intraretinal capillaries, like those of intracerebral capillaries, are joined by bands of tight junctions, forming a blood-retina barrier in the literal sense of the term. Capillaries in the ciliary body are leaky, but the ciliary epithelium prevents diffusion into the aqueous and vitreous humors, just as the choroid epithelium prevents diffusion into cerebrospinal fluid. Finally, substances in the sclera and choroid are unable to reach the retina because retinal pigment epithelial cells are also joined by tight junctions, forming a layer analogous to the arachnoid barrier; traffic between choroidal capillaries and photoreceptors is mediated by transport across the pigment epithelium.

Retinal Neurons and Synapses Are Arranged in Layers

The entire retina is conventionally described as a 10-layered structure, beginning with the pigment epithelium (Fig. 17-5; see also Fig. 17-14); five of these layers are the layers of cell bodies and synapses just mentioned. In naming these layers, the term nuclear refers to cell bodies and the term plexiform to synaptic zones. Inner and outer refer to the number of synapses by which a structure is separated from the brain, so that, for example, photoreceptors are “outer” with respect to bipolar cells. From outside in, the 10 layers of the retina are as follows.

Figure 17-5 Light micrograph of human retina. The entire retina is only 200 to 300 μm thick; the tiny speck at the bottom of the photo shows the actual size of this piece of retina. GCL, ganglion cell layer; ILM, inner limiting membrane; INL, inner nuclear layer; IPL, inner plexiform layer; IS, inner segments; NFL, nerve fiber layer; OLM, outer limiting membrane; ONL, outer nuclear layer; OPL, outer plexiform layer; OS, outer segments; RPE, retinal pigment epithelium.

(Courtesy Dr. Allen L. Bell, University of New England College of Osteopathic Medicine.)

2. Rods and cones are the two different types of vertebrate photoreceptors. Each consists of several regions (Fig. 17-6): an outer segment, an inner segment, a cell body, and a synaptic terminal. (Strictly speaking, rod or cone refers to only the outer segment plus the inner segment of a photoreceptor cell, but these terms are commonly used to refer to entire receptors.)

Figure 17-6 Electron micrographs of rods and cones. A, Scanning electron micrograph of the retina of a bullfrog. B, Electron micrograph of the photoreceptor layer of a rhesus monkey’s retina. This section was taken from a region near the fovea but not in it, so both rods and cones are plentiful. The outer limiting membrane (OLM) is actually a row of intercellular junctions. The insertion of the tips of rod outer segments into the pigment epithelial layer is apparent. C, cone nucleus; R, rod nucleus; RPE, retinal pigment epithelium.

(A, from Steinberg RH: Z Zellforsch 143:451, 1973. B, courtesy Dr. David Moran and Pamela Eller, University of Colorado Health Sciences Center.)

The outer segment of a rod is relatively long and cylindrical, whereas that of a cone (except in the fovea) is shorter and tapered (Figs. 17-6 and 17-7). Each type of outer segment is filled with hundreds of flattened membranous sacs, or disks. In cones, the interior of most of these disks is continuous with extracellular space, but in rods, almost all the disks have pinched off from the external membrane and are wholly intracellular. The major protein constituent of the outer segment membranes of both rods and cones is the visual pigment, which is called rhodopsin in rods. (There is no universally accepted name for the visual pigments of cones, and they are often referred to simply as cone pigments.) Hence photons traversing the outer segment of a rod or cone must pass through hundreds or thousands of sheets of membrane, each full of visual pigment molecules. As one might expect from this localization of visual pigment, the outer segment is the site of visual transduction; photons absorbed here cause a receptor potential that then spreads to the rest of the cell. The photosensitive portion of the receptor cells, oddly enough, is located in the part of the neural retina farthest removed from incoming light (i.e., the retina is inverted with respect to the path of light through it [Figs. 17-2 and 17-4]). This curious situation is universally true among vertebrates. However, this does not detract substantially from visual sensitivity or acuity, because the retina is thin (Fig. 17-5) and nearly transparent (Fig. 17-8), and because other anatomical modifications (discussed shortly) are found in the retinal area of greatest acuity.

Figure 17-7 Ultrastructural differences between the outer segments of rods and cones. A, General shape of peripheral rods and cones and of foveal cones dissociated from a human retina. B, Rod outer segment (cut off near the top to be the same length as the cone outer segment in C); note that some disks toward the base of the outer segment are open to the outside world, but most disks are pinched off and completely surrounded by cytoplasm. C, Cone outer segment; note that this outer segment tapers toward its apex (hence its name) and that all its disks are infoldings of the plasma membrane, with their interiors still continuous with extracellular space. IS, inner segment; N, nucleus in cell body; OS, outer segment; S, synaptic ending.

(A, from Ramón y Cajal S: Histologie due système nerveux de l’homme et des vertébrés, vol 2, Paris, 1911, Maloine. B and C, courtesy Dr. Richard W. Young, University of California at Los Angeles.)

Figure 17-8 An isolated human neural retina.

(Courtesy Dr. Dennis M. Dacey, University of Washington School of Medicine.)

Each outer segment is an elaborately specialized cilium that remains connected to its inner segment by a narrow ciliary stalk. The inner segments contain, among other organelles, a very prominent collection of mitochondria. These mitochondria supply the energy necessary for processes associated with transduction and for the synthesis of visual pigments. These pigments are continually renewed, being synthesized in the inner segment, transported through the ciliary stalk, and incorporated into disk membranes. “Old” disks at the apical ends of the outer segments of rods and cones are then phagocytosed by the pigment epithelium. (Certain types of retinal degeneration are caused by a defect in this renewal-phagocytosis process.)

As discussed later in this chapter, rods mediate low-acuity, monochromatic vision in dim light, whereas cones mediate high-acuity color vision, but require more light to do so.

8. The ganglion cell layer contains the cell bodies of the ganglion cells, whose dendrites ramify in the inner plexiform layer and whose axons leave the eye as the optic nerve. This cell layer is considerably thinner than either the outer or the inner nuclear layer in most retinal locations, reflecting the fact that there are about 5 million cones and about 100 million rods in a human retina, but only about 1 million ganglion cells. Clearly, a good deal of convergence is involved in retinal processing, but the convergence is not uniform across the retina. As discussed shortly, some regions are specialized for high spatial acuity and have little convergence, whereas other regions are specialized for high sensitivity and have a great deal of convergence.

Figure 17-24 Formation of center-surround receptive fields at the level of bipolar cells, using foveal cones and midget bipolar cells as examples. A, Formation of receptive field centers. In the dark, photoreceptors are depolarized and release glutamate onto the superficial synapses made by OFF-center bipolar cells (1) and onto the invaginating processes of ON-center bipolar cells (2) and horizontal cells (3). Because of the nature of the postsynaptic receptor molecules, glutamate hyperpolarizes the processes of ON-center bipolar cells and depolarizes the other two kinds of processes. Hence in the dark, ON-center bipolar cells are relatively hyperpolarized, and horizontal cells and OFF-center bipolar cells are relatively depolarized. Light in the receptive field center hyperpolarizes the cone (4), decreases glutamate release, and reverses all these polarizations: ON-center bipolar cells (as their name implies) depolarize (5), and the ganglion cells to which they project fire more rapidly; OFF-center bipolar cells hyperpolarize (6); and horizontal cells also hyperpolarize (7), but only moderately, because glutamate is still being released onto their other processes. B, Role of horizontal cells in formation of the antagonistic surround. Light delivered to cones surrounding the central cone in A causes a large hyperpolarization of horizontal cells (1) because of diminished glutamate release on many of their processes. This hyperpolarization spreads to the synaptic terminal of the central cone (2), in turn causing increased release of glutamate (as though it just got darker in the center of the receptive field), hyperpolarization of the ON-center bipolar cell (3), and depolarization of the OFF-center bipolar cell (4). The mechanism of this increased glutamate release is still being investigated, but it probably involves the effects of altered pH in the synaptic cleft on voltage-gated Ca²⁺ channels in the photoreceptor synaptic terminal.

Figure 17-25 Rod signals reach ganglion cells through a remarkable system of special amacrine cells and modifiable gap junctions. At scotopic levels (A), rod signals reach rod bipolar cells, which hyperpolarize in response to glutamate (so they depolarize in response to light). Rod bipolar cells terminate on processes of special amacrine cells, in turn depolarizing them. Gap junctions open between amacrine cell processes and the synaptic terminals of cone ON-center bipolar cells (green arrow), allowing rod signals access to this branch of the cone circuitry. Other processes of the same amacrine cells make inhibitory (glycine) chemical synapses on the synaptic terminals of cone OFF-center bipolar cells (red arrow) and also on dendrites of OFF-center ganglion cells. At mesopic levels (B), gap junctions between rod and cone terminals open (green arrows), and rod receptor potentials gain access to the cone circuitry described in Figure 17-24.

Visual information travels in several parallel streams, just as somatosensory information travels rostrally through the spinal cord and brainstem in multiple parallel pathways. In the case of the visual system, the axons of several anatomically and functionally distinct classes of ganglion cells share the same optic nerve in their course toward the brain. In the primate visual system, approximately 80% of all ganglion cells form a single class of small cells that are particularly responsive to the colors of visual objects and to details of their shapes. Some general aspects of the distinctive connections of this and other ganglion cell classes are mentioned later in this chapter.

The Retina Is Regionally Specialized

Cross sections through the retina do not have the same appearance at all locations. For example, no photoreceptors, interneurons, or ganglion cells are present at the optic disk, where the axons of ganglion cells leave the eye to form the optic nerve (Fig. 17-9). These axons originate near the vitreous, so they must turn posteriorly and traverse the retina before passing through the sclera. Because there are no photoreceptors at the optic disk, we are blind to any object whose image falls on this part of the retina. Although the blind spot can be demonstrated easily (Fig. 17-10), we have no awareness as we walk around a blank spot in visual space. One might think this is because the left eye can see the part of the visual field that falls on the right eye’s blind spot, and vice versa (see Fig. 17-32). This cannot be the explanation, though, because we are unaware of the blind spot even with one eye closed. The real reason is that the nervous system simply “fills it in.” We are actually quite skillful at this, and patients with damage to their visual systems can become blind in surprisingly large areas of their visual fields without being aware of it.

Figure 17-9 Light micrograph of a human optic disk, showing the absence of neuronal layers at this location. Arrows indicate bundles of optic nerve fibers passing through the lamina cribrosa, the perforated scleral zone at the optic disk. *, subarachnoid space surrounding the optic nerve; GCL, ganglion cell layer; INL, inner nuclear layer; ONL, outer nuclear layer; RPE, retinal pigment epithelium.

(Courtesy Dr. Allen L. Bell, University of New England College of Osteopathic Medicine.)

Figure 17-10 How to demonstrate your right eye’s blind spot to yourself. A, Close your left eye, hold the book at arm’s length, stare fixedly at the spot on the left side of the figure, and slowly move the book toward you. At some point about a foot from your face, the bearded gentleman’s head will disappear. B, Demonstration of how the CNS “fills in” the blind spot. Again, close your left eye, stare at the black spot with your right eye, and move the book slowly toward you. When the image of the hole in the striped pattern falls on your blind spot, your brain will try to convince you that there are stripes where none exist.

(A, based on a technique of King Charles II, as recounted by Rushton WAH: Vision Res 19:255, 1979.)

Beginning near the lateral edge of the optic disk is a circular portion of the retina, about 5 mm in diameter, in which many of the cells contain a blue-absorbing pigment. This gives the area a yellowish color (Fig. 17-8) when examined with appropriate illumination and has led to its being called the macula lutea (Latin for “yellow spot”), usually shortened to macula. In the center of the macula is a depression about 1.5 mm in diameter, called the fovea, which is particularly rich in cones. In the central part of the fovea is a pit, only about 350 μm across, that contains only elongated cones (no rods) and is directly in line with the visual axis (Fig. 17-11). The central fovea is specialized for vision of the highest acuity; all the neurons and capillaries that are present elsewhere (and that light would otherwise traverse before reaching the receptors) are collected around the edges of the fovea. Specialized interneurons called midget bipolar cells receive their inputs from individual foveal cones. These bipolars in turn contact individual midget ganglion cells, so that an anatomical basis for highly detailed foveal vision is maintained.^*

Figure 17-11 Fovea of a rhesus monkey. Note that all retinal elements (except the photoreceptors, which are all cones in the center of the fovea) are displaced to either side so that light needs to pass through only the outer nuclear layer before reaching the cones. The nerve fiber layer is scanty in this region because the axons of more laterally placed ganglion cells arc around the fovea on their way to the optic disk.

(From Fine BS, Yanoff M: Ocular histology, ed 2, New York, 1979, Harper & Row.)

The fovea is one extreme in a changing rod-cone distribution across the retina (Fig. 17-12). The packing density of cones decreases sharply outside the fovea, whereas that of rods increases, reaching a maximum just outside the macula. From here to the edge of the retina, the cone density remains at a low level, and the rod density slowly declines as well (Fig. 17-13). Given the properties of rods and cones, it follows from these distributions that the fovea is used for high-acuity color vision in reasonably bright light, whereas extrafoveal regions function at lower light levels.

Figure 17-12 Differential distribution of rods and cones in the human retina. A and C, Standard histological sections parallel to the long axes of photoreceptor inner and outer segments in the fovea (A) and the midperipheral retina (C). B and D, The array of photoreceptors in comparable areas of another retina viewed end-on, using a special video microscopy technique (Nomarski differential interference contrast) that allows focusing on a particular cross-sectional plane of the sample. In this case, the plane of focus is one that cuts through the photoreceptor inner segments at the level indicated by the arrowheads in A and C. In the fovea (B), all the inner segments are of closely packed, slender cones, whereas in the midperipheral retina (D), the inner segments of fatter cones are interspersed among the rod inner segments. Scale marks in C (applies also to A) and D (applies also to C) = 10 μm.

(Modified from Curcio CA et al: J Comp Neurol 292:497, 1990.)

Figure 17-13 Differential distribution of rods and cones in the human retina. A, Funduscopic view of the left retina. Arteries and veins emerge from the optic disk (*) and arc around the fovea (F). B and D, Distributions of cones (B) and rods (D) in an area of retina comparable to that shown in A. Note the absence of photoreceptors in the optic disk (*), the foveal concentration of cones (shown enlarged in C), and the perifoveal concentration of rods. The scale at the lower left shows the number of cells per mm².

(A, courtesy Dr. Christine A. Curcio, University of Alabama at Birmingham. B to D, modified from Curcio CA et al: J Comp Neurol 292:497, 1990.)