Chapter 20
The Visual System
Neural Retina and Pigment Epithelium
Processing of Visual Input in the Retina
Outer and Inner Plexiform Layers
Optic Nerve, Chiasm, and Tract
Visual Fields Correlated with Visual Structures as Seen in Magnetic Resonance Imaging
Magnocellular and Parvocellular Layers
Ipsilateral and Contralateral Layers
Functional Organization of Visual Cortex
Receptive Field Properties of Cortical Neurons
Vision is the sensory modality that perhaps captures the imagination more than any other. Phrases such as “He is the apple of my eye,” or “Her eyes flashed with anger,” or “I see what you mean” are common in the language and literature of most cultures and date back thousands of years. Furthermore, because of the way the nervous system converts optical images into neural signals and eventually visual experiences, it is technically easier to study the visual system than other sensory systems. The visual system has consequently been studied in greater depth, in both its anatomy and its physiology, than other sensory systems, and the neural mechanisms by which physical energy in the environment is translated into psychological perceptions are better understood in the visual system than in any other sensory system. It turns out that many of the basic anatomic features and physiologic properties of the visual system, especially at the level of the cerebral cortex, are shared with other sensory systems. This chapter presents the visual system both as a sensory system important in its own right, particularly with respect to its importance in neurologic diagnosis, and as a convenient example of some basic principles of neural processing that are found in many neural systems, including sensory, motor, and associational systems.
OVERVIEW
Like other sensory systems, the visual system creates a location-coded (visuotopic) “map” of its sensory field (the visual world) that is preserved at all levels. Light information is received by the retinal photoreceptors, and the initial processing of the visual signal occurs in the retina. Although the retina projects to several diencephalon and midbrain structures, most retinal axons terminate in a thalamic relay nucleus, the lateral geniculate nucleus, which in turn innervates the primary visual cortex, a region in the occipital lobe. From there, visual information is sent to a number of visual association areas in the occipital, temporal, and parietal lobes.
ANATOMY OF THE EYE
The human eye forms an optical image of an individual’s surroundings and focuses that image on an array of approximately 125 million photoreceptors (rods and cones) that are located in the neural retina. The image is inverted and reversed by the lens. The anatomy of the eye is summarized here.
Cornea
The cornea provides a transparent protective coating for the optical structures of the eye (Fig. 20-1). Its lateral margin is continuous with the conjunctiva, a specialized epithelium covering the “white” (sclera) of the eye. Although the conjunctiva and sclera have a blood supply (most evident when the eyes are irritated), the central cornea is normally not vascularized.
Figure 20-1. Cross section of the human eye. The gray arrow shows the path of light through the optical apparatus.
A variety of conditions may affect the cornea and, by disturbing the transmission of light through the cornea, degrade the quality of the visual image. Damage to the cornea may occur in chronic infections of herpesvirus, of Chlamydia trachomatis, or of the bacteria that cause conjunctivitis. Trauma may, of course, cause permanent damage to the cornea. In addition, various metabolic diseases may result in crystal deposits or other opacities in the cornea.
Chambers of the Eye
Just behind the cornea is the fluid-filled anterior chamber, which is bound posteriorly by the iris and the opening of the pupil (Fig. 20-1). A second fluid-filled space, the posterior chamber, is bound anteriorly by the iris and posteriorly by the lens and its encircling suspensory ligament (zonule fibers). Fluid is continuously produced by the epithelium over the ciliary body around the rim of the posterior chamber and flows through the pupillary opening into the anterior chamber. It then drains into a set of modified veins, the canals of Schlemm, that are located around the rim of the anterior chamber in the angle where the iris meets the cornea. Because the suspensory ligament encircling the lens consists of discrete strands, the fluid in the posterior chamber is in contact with the vitreous body, the gelatinous mass that fills the main space of the eyeball between the lens and the retina.
Any condition that obstructs the outflow of fluid via the canals of Schlemm can lead to glaucoma, a buildup of fluid and hence pressure in the entire eyeball, with resultant damage to the retina and optic nerve and eventual blindness. Patients with glaucoma often comment that their vision is blurred but not dimmed. A normal amount of light reaches the retina, but the progressive loss of photoreceptors causes blurring of the visual image. Damage proceeds from the periphery of the retina toward the central region where the fovea is located. In most cases of glaucoma (about 90%), the angle between the iris and cornea is normal (open-angle glaucoma), and the cause of the increase of pressure is unknown. In about 5% of patients, the angle between cornea and iris is abnormally acute (closed-angle glaucoma) and blocks the normal flow of fluid. In the remaining cases, the canals of Schlemm are blocked by debris from infection, complications of diabetes, or hemorrhage into the anterior chamber. When the intraocular pressure is above 20 mm Hg, optic nerve damage is a concern. The resulting visual loss proceeds from partial (in the periphery first) to total.
Iris
The iris is a pigmented structure lying directly anterior to the lens (Fig. 20-1). The connective tissue, or stroma, of the iris contains melanocytes that reflect or absorb light to give the iris its characteristic color. Also embedded in the stroma are the circumferentially organized sphincter muscle of the iris and the radially arranged dilator muscle (Fig. 20-1).
The innervation of the iris sphincter, which closes the pupil, is parasympathetic. This pathway begins with preganglionic neurons whose cell bodies lie in the Edinger-Westphal preganglionic nucleus and whose axons terminate in the ciliary ganglion. Axons of postganglionic ciliary ganglion neurons, in turn, end as neuromuscular synapses on the sphincter muscle and release acetylcholine. When activated, this pathway results in a reduction in pupil diameter, or miosis.
The innervation of the iris dilator, which opens the pupil, is sympathetic. The pathway begins with preganglionic neurons whose cell bodies lie in the intermediolateral cell column of the spinal cord at upper thoracic levels and whose axons terminate in the superior cervical ganglion. Axons of postganglionic superior cervical ganglion neurons, in turn, end as neuromuscular synapses on the dilator muscle and release norepinephrine. When activated, this pathway results in an increase in pupil diameter, or mydriasis. This phenomenon is a measure of the general state of the sympathetic tone. Anger, pain, or fear may result in an enlargement of the pupil in the absence of a change in lighting conditions. The pupillary light reflex, a contraction of the pupil in response to light, is used to assess the function of the nervous system, particularly at midbrain levels (see Chapter 28).
The circumference of the pupillary margin changes by a factor of six. This proportional change in muscle length is greater than any other in the human body. To accomplish this change, acetylcholine is released onto both the sphincter and dilator muscles. The effect is to activate muscarinic receptors that depolarize sphincter muscle cells and cause contraction. In addition, acetylcholine released by collaterals onto the dilator muscle mediates presynaptic inhibition of norepinephrine release and blocks dilator contraction. Thus, as the sphincter contracts, the dilator relaxes, strengthening the pupillary response to light.
Lens
The lens is a clear structure that focuses light on the retina (Fig. 20-1). The lens of the eye is a simple convex lens that inverts and reverses the image on the retina. Mechanisms that change the curvature of the lens are discussed in detail in Chapter 28.
Beginning at about the age of 40 years, the lens begins to lose its elasticity so that the shape it adopts when relaxed is more flattened than earlier in life. This change reduces the affected person’s ability to focus on near objects, a condition called presbyopia. Reading or bifocal corrective lenses are prescribed to aid the patient in performing tasks requiring close, detailed vision.
Cataract
Opacities in the lens, known as cataracts, are relatively common and can be seen as a cloudiness of the lens. Cataracts may be caused by congenital defects (e.g., secondary to maternal infection with rubella), persistent exposure to ultraviolet light, diabetes, high doses of some medications, radiation therapy, or poorly understood mechanisms that occur in aging. Current therapy consists of replacement of the lens with an inert plastic prosthesis, restoring sight but with a concomitant loss of accommodation.
Uvea
The iris, ciliary body, and choroid make up the vascular tunic of the eye, also called the uvea. The choroid is a highly vascularized, pigmented tissue layer lying between the retinal pigment epithelium and the sclera, the tough outer coating of the eye. Uveitis is an inflammation of these structures, often secondary to eye injury.
NEURAL RETINA AND PIGMENT EPITHELIUM
The inner surface of the posterior aspect of the eye is covered by the retina, which is composed of the neural retina and the retinal pigment epithelium (Fig. 20-2). In describing the layers and cells of the retina, it is common to use the terms inner and outer. Inner refers to structures located toward the vitreous (i.e., the center of the eyeball), whereas outer is used in reference to structures located toward the pigment epithelium and choroid.
The retinal pigment epithelium is a continuous sheet of pigmented cuboidal cells bound together by tight junctions that block the flow of plasma or ions. Its functions are as follows: (1) it supplies the neural retina with nutrition in the form of glucose and essential ions; (2) it protects retinal photoreceptors from potentially damaging levels of light; and (3) it plays a key role in the maintenance of photoreceptor anatomy via phagocytosis.
The neural retina contains the photoreceptors and associated neurons of the eye and is specialized for sensing light and processing the resultant information. The photoreceptors absorb quanta of light (photons) and convert this input to an electrical signal. The signal is then processed by retinal neurons, as discussed further on. Finally, the retinal neurons called ganglion cells send the processed signal to the brain via axons that collectively form the optic nerve.
The contact between the neural retina and the pigment epithelium is the adult remnant of the ventricular space of the developing eye cup. As such, it is mechanically unstable. This instability is demonstrated in a retinal detachment, in which the neural retina tears away from the pigment epithelium. Retinal detachment is more commonly seen in male patients and may result from a range of factors, such as trauma to the orbit or head, sequela to cataract surgery, genetic predisposition, degenerative diseases of the eye or optic nerves, and aging. Because photoreceptors are metabolically dependent on their contact with pigment epithelial cells, a detached retina must be repaired to avoid further damage. The detached part of the neural retina is reattached to the pigment epithelium by surgical procedures. The degree of functional recovery in the reattached part of the retina depends on its location. It also depends on how soon the reattachment is performed after the injury.
The neural retina has seven characteristic layers (Fig. 20-2). From outer to inner they are (1) a layer containing the photoreceptor cell outer and inner segments; (2) an outer nuclear layer, consisting of the nuclei of photoreceptor cells; (3) the outer plexiform layer, consisting of the synaptic connections of photoreceptors with second-order retinal cells; (4) the inner nuclear layer, containing somata of second-order and some third-order retinal cells; (5) the inner plexiform layer, another area of synaptic contact; (6) the ganglion cell layer, containing the cell bodies of the ganglion cells; and (7) the nerve fiber layer (or optic fiber layer), composed of the axons of the ganglion cells. These axons converge at the optic disc to form the optic nerve. Layers 2 through 7 are flanked by a pair of limiting membranes, which consist of glial cell processes joined by tight junctions. The outer limiting membrane is located between layers 1 and 2, and the inner limiting membrane is located between the nerve fiber layer and the vitreous.
The photoreceptor outer segments interdigitate with the melanin-filled processes of pigment epithelial cells (Fig. 20-2). These processes are mobile, and they elongate into the pigmented layer when the light is bright (photopic conditions) and retract when the light is dim (scotopic conditions). This mechanism combines with contractions of the iris to protect the retina from light conditions that would otherwise damage the photoreceptors. The iris, pigment epithelium, and circuitry of the retina all contribute to the eye’s ability to resolve the visual world over a wide range of light conditions.
The blood supply of the neural retina arises from branches of the ophthalmic artery; these branches are the central artery of the retina and the ciliary arteries. The central artery is usually the first branch of the ophthalmic, passes rostral and inferiorly adjacent to the dural sheath, and then enters the sheath and the optic nerve about 1.25 cm caudal to the bulb of the eye. After entering the eyeball, it branches out from the optic nerve head to serve inner portions of the neural retina. The ciliary arteries penetrate the sclera around the exit of the optic nerve and feed the choriocapillaris (a portion of the choroid), which in turn provides nutrients to the outer portions of the neural retina.
PHOTORECEPTOR CELLS
The rods and cones of the retina are responsible for photoreception, the process by which photons are detected and the information is transduced into an electrochemical signal. There are two basic types of photoreceptors, rods and cones (Figs. 20-3 and 20-4), although a special class of ganglion cell (melanopsin-containing ganglion cell) may be considered a third type of photoreceptor (see later). Rods and cones have the same general overall design. Light is detected and transduced in an outer segment that points toward the pigment epithelium. A narrow stalk, the cilium, connects the outer segment to a second expanded region called the inner segment, which contains mitochondria and produces the energy that maintains the cell. The cilium contains nine pairs of microtubules emanating from a basal body located in the inner segment. The nucleus and perikaryon of the cell are found in the outer nuclear layer; finally, the cell terminates in the outer plexiform layer in an expansion that makes synaptic contacts with neurons. This synaptic expansion is called the spherule in rod cells and the pedicle in cone cells. Both rod and cone synaptic terminals contain a characteristic dark sheet of protein called the synaptic ribbon. This structure may act as a “conveyor belt,” organizing vesicular release of transmitter.
Rods
Rod cells are named for the shape of their outer segment, which is a membrane-bound cylinder containing hundreds of tightly stacked membranous discs (Fig. 20-3). The rod outer segment is a site of transduction. Photons travel through cells of the neural retina before striking the membranous discs of the rod outer segment. Molecules of rhodopsin within these membranes undergo a conformational change and along with transducin and phosphodiesterase induce biochemical changes in the rod outer segment, which reduce levels of cyclic guanosine monophosphate (cGMP). In the dark, cGMP levels in the rod outer segment are high. This cGMP mediates a standing sodium current. At rest, in the dark, sodium ions flow into the rod outer segment. This high resting level of sodium permeability results in a relatively high resting potential for rod cells, about −40 mV. These sodium channels of the outer segment membrane, which are normally open, close in response to increased calcium or a reduction in cGMP. This drives the membrane potential away from the sodium equilibrium potential and toward the potassium equilibrium potential, and the rod cell is hyperpolarized in response to a light stimulus (Fig. 20-3). Note that photoreceptors are the only sensory neurons that hyperpolarize in response to the relevant stimulus.
The hyperpolarization of the rod outer segment propagates passively (i.e., without firing an action potential) through the perikaryon to the rod spherule. In the absence of light, the photoreceptor terminals constantly release the transmitter glutamate at these synapses. The arrival of a light-induced wave of hyperpolarization causes a transient reduction in this tonic release of glutamate. As explained further on, this event can depolarize some of the cells that receive synapses from photoreceptor terminals while hyperpolarizing others.
Rhodopsin molecules are capable of a huge but finite number of photoisomerization events. Rather than replace individual rhodopsin molecules, every morning the distal one tenth of the outer segment is broken off and phagocytosed by the pigment epithelium. Through this process of rod shedding, the outer segment is constantly renewed. New discs are formed at the base of the outer segment and move outward so that the shed discs are replaced. In this way, the rod remains a constant length and the outer segment is renewed about every 10 days.
Cones
Like rod outer segments, cone outer segments also consist of a membranous stack (Fig. 20-4). Unlike in rods, however, these stacks of cone membranes are of constantly decreasing diameter (from cilium to tip), giving the cell its characteristic shape. Also, they are not enclosed within a second membrane but are open to the extracellular space adjacent to the pigment epithelium (Fig. 20-4).
The process of transduction in cones is generally similar to that in rods. Cone opsin absorbs photons and undergoes a conformational change, resulting in a hyperpolarization of the cell membrane (Fig. 20-4). This hyperpolarization propagates passively to the cone’s synaptic ending, the cone pedicle, in the outer plexiform layer. Cone pedicles and rod spherules both contain synaptic ribbons surrounded by vesicles, but cone pedicles are larger (Fig. 20-4). Serial-section electron microscopy has shown that the synaptic ribbons are actually a single extensive sheet of protein. Like rods, cones release the neurotransmitter glutamate tonically in the dark and respond to light with a decrease in glutamate release.
There are three types of cones, each tuned to a different light wavelength (Fig. 20-5). L-cones (red cones) are sensitive to long wavelengths, M-cones (green cones) to medium wavelengths, and S-cones (blue cones) to short wavelengths. Because any pure color represents a particular wavelength of light, each color will be represented by a unique combination of responses in the L-, M-, and S-cones.
If one of these cone types is absent because of a genetic defect in the corresponding opsin, the affected person will confuse certain colors that look different to visually normal individuals and is said to be color blind. It is better, however, to think of this condition as “color confusion” because the patient can still see all colors of the visible spectrum; it is the ability to distinguish certain colors that has been lost. Because the genes for the L-cone (red-absorbing) and M-cone (green-absorbing) opsins are located on the X chromosome, color blindness is more common in men. Alteration of the gene for the S-cone (blue-sensitive) pigment, which is located on an autosome, is much rarer. The inability to detect a pure red is known as protanopia, and inability to detect green is known as deuteranopia.
Macula and Fovea
At the posterior pole of the eye is a yellowish spot, the macula lutea, the center of which is a depression called the fovea centralis (Fig. 20-6). Near the fovea, the inner retinal layers become thinner and eventually disappear so that at the bottom of the foveal pit, only the outer nuclear layer and photoreceptor outer segments remain. This allows a maximum amount of light to reach the photoreceptors with optimal fidelity.
Most of the visual input that reaches the brain comes from the fovea. Cones, which are responsible for color vision, are the only type of photoreceptor present in the fovea. In contrast, rods, which are most sensitive at low levels of illumination, are the predominant photoreceptors in the periphery of the retina. The visual world is a composite formed from a succession of foveal images carrying form and color information supplemented with input from the peripheral retina carrying motion information.
RECEPTIVE FIELDS
The receptive field of a visually responsive neuron is defined as that region of the visual world in which a stimulus of the proper characteristics will influence the activity of the neuron. The influence may be either excitatory or inhibitory. Some neurons will exhibit an excitatory influence when the stimulus is in one location and an inhibitory influence when the stimulus is in a nearby location. The receptive field of a neuron is the sum of the areas in which the stimulus affects the activity of that neuron.
In the early stages of visual information processing, receptive fields have a characteristic concentric center-surround organization. The receptive field is roughly circular (Fig. 20-7). Stimuli in the center of this circle tend to evoke one type of response (e.g., depolarization), whereas stimuli in the doughnut-shaped outer rim evoke the opposite response (e.g., hyperpolarization). In later stages of visual processing, in the visual cortex, receptive field properties are more complicated.
PROCESSING OF VISUAL INPUT IN THE RETINA
Among retinal cells, only retinal ganglion cells have voltage-gated sodium channels on their axonal membranes. As a result, only ganglion cells use action potentials to carry information. So-called calcium spikes resulting from an increase in calcium permeability are seen in amacrine cells. All other retinal cells use only graded potentials to process information.
The receptive field properties of each retinal cell depend on the processing of information passing through the neurons between the photoreceptor and the retinal cell in question. For example, a bipolar cell’s response is directly related to the activity of photoreceptors and horizontal cells (Figs. 20-7 and 20-8). As with all sensory systems, the structural, electrical, and synaptic properties of the cell are reflected in receptive field properties.
