light passes through, allowing for transmission of more of the light and virtual elimination of internal reflections that would otherwise compromise visual acuity [1–3].

Between the cornea and the lens is the iris. This structure provides an aperture that controls the amount of light that enters the eye and passes through to the retina. The iris is located between the two refractive surfaces, reducing distortion of the entering light. The iris is pigmented, and the opening of the iris is termed the pupil. This opening is reduced in brighter illumination and increased in dimmer illumination to provide sufficient stimulation for the retinal cells.

Directly behind the cornea is a fluid-filled chamber; the fluid is called the aqueous humor. Fluid is continually secreted into this chamber and continually drained from it. In certain medical conditions, the drain rate of fluid is reduced, and pressure can build. This occurs in many types of glaucoma, in which the increase in pressure is gradual over time and can be controlled to some extent by medication that reduces fluid production. An uncontrolled elevation of pressure causes a gradual loss of vision due to damage to the cells at the back of the eye that form the optic nerve [2].

While the aqueous humor fluid helps maintain the structure and curvature of the cornea, it is the gelatinous vitreous humor that maintains the full shape of the orb of the eye. The vitreous fills the region behind the lens and in front of the retina and provides sufficient pressure to keep the round shape of the eye.

Optically, then, light passes through the cornea, aqueous humor, iris, lens, and vitreous humor on its path to the retina. The cornea and lens are the refractive elements, with the lens the only adjustable one, and the iris modulates the amount of light that passes.

If there are aberrations in the shape of the eye or of the cornea, then distortion of vision occurs. When the cornea is not radially symmetric, astigmatism results, by which the focus at one angle differs slightly from the focal distance at another angle. If the overall shape of the cornea is rounder or flatter, then the conditions of myopia (nearsightedness) or hyperopia (farsightedness) result because the focal distance is slightly different from what is needed to form a clear image on the retina. Thus, slight changes in the shape of the cornea, since it is the primary focusing element, result in deviations from normal focus.

For those who are myopic, the decrease in lens malleability seen in presbyopia has a delayed impact on vision compared to the hyperopic individual. The reason is simply that as the near point of vision moves further from the eyes, if one has started with a closer near point of vision (as is the case in myopia), then the effect is to move the near point to a normal reading distance, while for the normal sighted or hyperopic, it is to move the nearest point of vision to a distance further than is readily readable (indeed, one typically finds that the letters are too small when they are in focus, and so use of reading glasses or a magnifying lens is needed to compensate).

RETINAL PHOTORECEPTION

Photoreception has two major components: optical and biochemical. The optical component is primarily described in the preceding section, although there are critical retinal portions to this. The biochemical component occurs in the outer retina.

Fig. 2. The organization of the retina. (Courtesy of Dr. Helga Kolb.)

Photoreception Optics

Optically, light focused by the front of the eye is imaged onto the photoreceptor layer of the retina. The retina itself is a thin neural tissue that lines the inside orbit of the eye and is comprised of several layers of cells, as can be seen in Fig. 1. These cells are in repeating arrays, such that in any given area of retina, the same cell types are found in a similar arrangement. The optical arrangement is that light passes first through ganglion cells, then amacrine, bipolar, and horizontal cells before arriving at the photoreceptors, which make up the outer retina (see Fig. 2) [1–4].

The retinal layers are defined from the inner to outer regions of the eye, with the ganglion cell axon fibers the innermost layer of the retina and the photoreceptors and epithelium the outermost retinal layers.

Within the retina, there are two types of photoreceptors: The rod photoreceptors provide for our night vision and are exquisitely sensitive to small amounts of light; the cone photoreceptors provide color vision. Cone photoreceptors are responsive to one of three colors (red, green, or blue); combined, the relative intensities of these three primary colors that we can see allow us to determine the color of any object and to see the full spectrum of the rainbow. This feature of only detecting three colors is why we can see all colors when we look at an LCD (liquid crystal display) screen, which is also only comprised of red, green, and blue (RGB), or at a magazine photo, which is typically made from cyan, magenta, and yellow (the complementary colors to RGB) along with black. The central part of the retina, called the fovea, contains a very high number of cone photoreceptors packed into a very small space, about 160,000 cone photoreceptors per square millimeter. This high density of cones is why when we look

straight at an object we can make out a large amount of detail. The cones in the fovea then provide our highest visual acuity, which is 0.017° (300 rad, or 1.03 arc minute) of our visual field. This works out to be a 19-inch object a mile away or the size of the pixels on a television or LCD monitor at normal viewing distance. A simple exercise to observe this is to view a computer monitor at a close distance and note that you can see the individual pixels, while at normal distance they are indistinguishable [1, 3].

The fovea provides this high acuity for the central 2° of our visual field. Within this region, there is a pit in the retina as the other cells are angled to the sides of the fovea, eliminating these cells from the path of the light onto the cones. Although the retinal neurons are transparent, for the centralmost vision, the small refraction that the cells create would decrement acuity slightly; thus their angling away from the fovea removes this potential detriment, retaining our crisp vision [1, 3].

Away from the fovea, there is a mixture of rod and cone photoreceptors, and the acuity is much more limited, although the sensitivity to low light levels is higher due to the presence of rods. One can observe this on a dark night, such as when something catches your eye and you turn to look at it, but it is not as bright as when seen in the periphery of one’s vision.

Outside of the neural retina lies the retinal pigment epithelium (RPE). This RPE has two essential functions for photoreception, one optical and the other biochemical. Optically, the RPE cells are black, and they surround the outer segments of the photoreceptors. This means that any light that passes around a photoreceptor is absorbed by the RPE. Thus, no light is reflected back onto the retina. This black curtain keeps us from seeing halos around objects and is therefore essential for high acuity. Notably, in nocturnal animals, such as cats, the epithelium is reflective, allowing them to capture every bit of light as they reflect the photons that are not captured in the first pass through. Their vision in dim light is thus very good, but their acuity is not as high as it is for humans due to this trade-off [5, 6].

Photoreception Biochemistry

The other key function of the RPE for photoreception is in regeneration of the visual pigment of the photoreceptors. For this, the RPE cells use vitamin A. The RPE exchanges and renews the photosensitive molecule from the photoreceptors, creating an intimate collaboration between these two cells. Hence, the photoreceptors rely on the RPE for both optical purposes and biochemical function.

Photoreception takes place in the outer segments of the photoreceptors. Photoreceptors are segmented into three regions: the outer segment, which is packed with photosensitive molecules; the inner segment, which contains the cell nucleus and a large amount of mitochondria to generate the energy for this photoreception; and the synaptic terminal, which communicates to the next cells in the visual system.

The biochemical process of photoreception is referred to as phototransduction. Molecules of visual pigment called opsin are embedded within the membrane of the rods and cones. Indeed, the rods and cones have an elaboration of membrane in their outer segments, with the cones having membrane folded over and over on itself and the rods containing a stack of membranous disks, which look much like a large stack of pancakes, within a sleeve of rod membrane. All this membrane is loaded with opsin

molecules (called rhodopsin in the rods), and these opsins absorb light of a specific range of wavelengths. Rhodopsin absorbs light of about 500 nm, while cone opsins absorb light of 420, 530, and 560 nm (blue, green, and red, respectively). These are the peak wavelengths, meaning that at these colors the opsin molecules are maximally stimulated. They absorb light 50 nm or more greater and lesser than their optimal color, but less strongly, so their response to light decreases as the color is further from their optimal wavelength [1, 4, 7].

When light is absorbed by rhodopsin, the light energy is absorbed by the portion of the molecule called retinal. This retinal is what is regenerated from vitamin A. When retinal absorbs light, its shape changes from a bent form to a straight form (from 11-cis retinal to all-trans retinal). This change in shape begins a cascade of events that result in a change in the voltage across the membrane of the photoreceptor.

Briefly, the stimulation of rhodopsin (changing the shape of retinal) results in activation of a molecule called transducin. Transducin is a guanosine triphosphate (GTP)-dependent protein (also called a G protein, part of a family of signaling molecules within many cells). The activation of transducin in turn activates an enzyme called phosphodiesterase. Phosphodiesterase is an enzyme that catalyzes a reaction in which cyclic guanosine monophosphate (cGMP; a signaling molecule within cells) is broken down to GMP. While the cyclic form of GMP is a signaling molecule, the noncyclic form is not. The removal of cGMP from photoreceptors results in a change in the membrane potential of the cells [7].

Photoreceptors have a collection of membrane-spanning channels that allow specific ions to pass through. One of these channels is specific for Na+ ions (sodium, a positively charged ion). This channel requires the presence of cGMP in the cell for its gate to open and Na to travel through. Since cells have more Na outside than inside, when the Na gate is open, the positively charged Na ions enter the cell, making the cell more positive in charge than it had been. These cGMP-gated Na channels then are open in the dark but become closed when the cells see light. Thus, when stimulated by light, photoreceptors become more negatively charged. This change in their membrane voltage is the first electrical sign that we have seen the light and is communicated to the next cells in the retina [1, 4].

Membrane Voltages

The voltage across the membrane of a cell is a standard feature of all cells of the nervous system, and it is the change in this membrane voltage that is used by neurons to process and transmit information. Thus, for all neurons, small changes in their membrane voltage are elicited by incoming information, with the incoming information arising from other neurons or from sense organs. These voltage changes (additive or subtractive, as some changes are positive charges and some are negative charges) result in a net change to the cell’s membrane voltage. In certain neurons, when this excursion in the membrane voltage reaches a threshold voltage level, the cell creates a large spike in its membrane voltage called an action potential. The action potential is regenerative, so the electrical spike travels along the thin tubular extension of the neuron called the axon and travels along this axon at a high rate of speed (over 100 m/s in some cells).

The amount of communication between neurons is determined in large part by the size of the change in the membrane voltage of the first cell. Now, while the change in