The Visual System

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 an inflated 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.

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 ( Clinical Focus Box 17.1 ).

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. Therefore, for nonaquatic vertebrates such as humans, most of the refraction occurs at the air-water interface at the front surface of the cornea ^b

b Fish and other aquatic animals obviously cannot use this mechanism. Instead, they have much larger, more spherical lenses, as well as adaptations to increase the difference in refractive index between the lens and the intraocular fluid.

; its curved shape, maintained by intraocular pressure, accounts for humans’ ability to see 90 degrees or more to the side (see Fig. 17.32 ).

It is possible to 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. The human lens is suspended by strands of connective tissue called zonules (see 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. Therefore, 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 humans have useful vision, from starlight to bright sunlight, is an astonishing 10 ¹² 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 (see 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. ^c

c Signs of this optic cup origin are found in many species, including many fish, amphibians, and some mammals.

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 30-fold change in area, consistent with the idea that retinal mechanisms play the major role in adjusting visual sensitivity. ^d

d Continuing the camera analogy, the million million-fold range of light intensities over which humans have useful vision corresponds to about 40 f-stops (amount of light that enters based on shutter speed). Pupillary constriction accounts for only about 4 f-stops.

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 ).

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. 6.28 ) 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. Damage to the blood vessels due to things like diabetic retinopathy can result in loss of vision ( Clinical Focus Box 17.2 ).

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:

• 1.

  The retinal pigment epithelium is a single layer of polygonal, pigmented cells. One side of each cell adjoins the choroid, whose capillaries supply the avascular first two layers of the retina. The other side of each cell forms numerous fine processes that partially surround the outer portions of the receptor cells and obliterate the space that existed embryonically within the wall of the optic cup. Pigment epithelial cells are intimately involved metabolically with the photoreceptors, including the regeneration of the 11-cis retinal that is so important in the opsin receptors. They also play a role in absorbing light that has passed through the retina and form a tight junction between cells as part of the blood-retina barrier.

• 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.)

  

  The outer segment of a rod is relatively long and cylindrical, whereas that of a cone (except in the fovea) is shorter and tapered (see 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 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. ) Therefore 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 may be expected 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 [see 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 (see Fig. 17.5 ) and nearly transparent ( Fig. 17.8 ), and because other anatomical modifications (discussed later) are found in the retinal area of greatest acuity.

  
  

  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 ( Clinical Focus Box 17.2 ). (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.

• 3.

  The outer limiting membrane was so named because it has the appearance of a distinct line when viewed with a light microscope. However, electron microscopy reveals it to be a row of intercellular junctions (see Fig. 17.6B ). Elongated specialized glial cells called Müller cells span almost the entire retina, ending distally at the bases of the inner segments of the rods and cones. Here, adjacent Müller processes and inner segments are joined by junctional complexes, which collectively form the outer limiting membrane.

• 4.

  The outer nuclear layer consists of the cell bodies of the rods and cones.

• 5.

  The outer plexiform layer is the relatively thin synaptic zone in which receptors terminate on horizontal and bipolar cells and in which processes of horizontal cells spread laterally. The rods and cones synapse on separate subpopulations of bipolar cells and on different regions of some horizontal cells (see Figs. 17.24 and 17.25 ).

• 6.

  The inner nuclear layer contains the cell bodies of all the retinal interneurons as well as those of the Müller cells. The nuclei of horizontal cells are found near its distal edge, those of bipolar cells in the middle, and those of amacrine cells near its proximal edge. Bipolar cells conduct visual information through this layer, projecting to the second synaptic zone.

• 7.

  The inner plexiform layer is the relatively thick synaptic zone in which bipolar cells terminate on amacrine and ganglion cells, and processes of amacrine cells spread laterally. The actual pattern of interconnections is somewhat more complex than that shown in Fig. 17.4 . The amacrine cells provide one example of this added complexity: based on neurochemical and anatomical characteristics, more than 30 different types, each presumed to have a somewhat distinctive function, have been described.

• 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 later, 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.

  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.

• 9.

  The nerve fiber layer is the collection of axons of ganglion cells that converge like spokes toward the optic disk or optic papilla (located posteriorly and slightly medial to the midline of the eye [see Fig. 17.2 ]), where they form the optic nerve. The central retinal artery, a branch of the ophthalmic artery, traverses the optic nerve and enters the eye at the optic disk. Therefore the retina has a dual blood supply, with the outer two layers supplied by the choroidal circulation (also fed by the ophthalmic artery) and the inner layers by the central retinal artery.

• 10.

  The inner limiting membrane is a thin basal lamina interposed between the vitreous and the proximal ends of the Müller cells.

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, humans 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 ), as we walk around we have no awareness of a blank spot in visual space. Some may 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 humans are unaware of the blind spot even with one eye closed. The real reason is that the nervous system simply “fills it in.” Humans are actually 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.

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 (see 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, which 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 an anatomical basis for highly detailed foveal vision is maintained. ^f

f Someone may think it advantageous to continue the anatomical specializations of the fovea, such as small, tightly packed photoreceptors and no convergence, throughout the retina; this would give us highly detailed vision over our entire field of view. However, as Wässle and Boycott point out ( Physiol Rev 71:447, 1991), foveal vision requires so much cerebral cortex (see Figs. 17.29 and 17.35 ) that using foveal specializations throughout the retina would necessitate 100 times as much cerebral cortex as we presently have available in the entire cerebrum. Instead, we use a very small fovea, together with precisely controlled eye movements that allow us to aim it at objects of interest (see Chapter 21 ).

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 (see Clinical Focus Box 17.2 ).

Recently developed tomographic techniques allow retinal layers and regional specializations to be visualized in living, intact eyes ( Box 17.1 and Fig. 17.14 ).

Photopigments Are G Protein–Coupled Receptors That Cause Hyperpolarizing Receptor Potentials

Rhodopsin and cone pigments are members of the same family of G protein–coupled receptors that mediate many postsynaptic effects and some other sensory transduction processes, such as olfaction. In the case of rods and cones, the ligand of the receptor protein opsin, rather than being a neurotransmitter or an odorant, is a vitamin A derivative (11- cis retinal) that enables the photopigments to absorb visible light. Slight differences among the opsins of rods and each of the three types of cones result in differences in the wavelengths absorbed preferentially by each photopigment (see Fig. 17.19A ). The only effect of light in the phototransduction process is to isomerize 11- cis retinal to all- trans retinal, which shortly thereafter dissociates from opsin. Isomerization of retinal causes a conformational change in the opsin to which it is bound, and opsin in its altered conformation activates nearby molecules of transducin, a G protein ( Fig. 17.16 ). Each activated transducin in turn activates phosphodiesterase, an enzyme that hydrolyzes cyclic guanosine monophosphate (cGMP). This seemingly cumbersome process results in great amplification. Absorption of a single photon by one of the hundred million rhodopsins in a rod can activate dozens of transducins; each transducin-activated phosphodiesterase can hydrolyze about a thousand cGMP molecules per second.

The surface membranes of rod and cone outer segments contain cGMP-gated cation channels. In the dark, the cGMP concentration is relatively high, the cation channels are open most of the time, and a current carried mainly by Na ⁺ ions flows into the outer segment ( Fig. 17.17 ). As a result, rods and cones have a relatively depolarized resting potential of about −40 mV in the dark and release neurotransmitter (glutamate) at a steady rate onto processes of bipolar and horizontal cells. Light-induced hydrolysis of cGMP causes cation channels to close, the membrane hyperpolarizes toward the potassium equilibrium potential, and transmitter release declines. ^g

g In a sense, therefore, our photoreceptors are really “darkness receptors,” depolarizing and releasing more transmitter as the level of illumination decreases. Presumably because we evolved spending about half our time in light and half in darkness, this arrangement is not as metabolically inefficient as it sounds at first. There are even some fortuitous economies now that we spend more than half our time in the light.