How the Retina Works Much of the construction of an image takes place in the retina itself through the use of specialized neural circuits Helga Kolb he retina is a filmy piece of tissue, fixed in the photoreceptors’ opsin pro- Most other mammalian retinas also Tbarely half a millimeter thick, that teins, where this small molecule have a preponderance of rods, and the lines the inside of the eyeball. The tis- changes its conformation in response cones are often concentrated in special- sue develops from a pouch of the em- to photons, or packets of light. Once ized regions. In species such as cats bryonic forebrain, and the retina is retinal molecules are exposed to light and dogs, images focus to a central therefore considered part of the brain. and undergo their conformational specialized area, aptly called the area This most important part of the eye change, they are recycled back into the centralis, where cones predominate. has a basic structure similar to that of a pigment epithelium. This tissue be- The retinas of mammals such as rab- three-layer cake, with the bodies of hind the retina is usually very dark bits and squirrels, as well as those of nerve cells arrayed in three rows sepa- because its cells are full of melanin nonmammals like turtles, have a long, rated by two layers packed with granules. The pigment granules ab- horizontal strip of specialized cells synaptic connections. The retina in- sorb stray photons, preventing their called a visual streak, which can detect cludes both the sensory neurons that reflection back into the photorecep- the fast movement of predators. Pri- respond to light and intricate neural tors, which would cause images to mates as well as some birds have front- circuits that perform the first stages of blur. They also protect the cells from projecting eyes allowing binocular vi- image processing; ultimately, an elec- too much exposure to light radiation. sion and thus depth perception; their trical message travels down the optic eyes are specialized for good daylight nerve into the brain for further pro- Retina Design According to Lifestyle vision and are able to discriminate col- cessing and visual perception. All vertebrate retinas contain at least or and fine details. Primates and rap- Intuitively, one might expect that two types of photoreceptors—the fa- tors, like eagles and hawks, have a the surface of the retina (the layer ex- miliar rods and cones. Rods are gener- fovea, a tremendously cone-rich spot posed to the liquid in the eyeball’s vit- ally used for low-light vision and cones devoid of rods where images focus. reous chamber) would contain the for daylight, bright-colored vision. The Primates, in fact, have what is called sensory cells, the photoreceptors, but variations among animal eyes reveal a duplex retina, allowing good visual actually these cells lie at the very back adaptations to the different environ- discrimination in all lighting condi- of the retina; light rays must pass ments in which they live. Most fish, tions. The fovea contains most of the through the entire retina before reach- frog, turtle and bird retinas have three cones, packed together as tightly as ing pigment molecules to excite. This to five types of cones and consequently physically possible, and allows good is because the pigment-bearing mem- very good color vision. Keep in mind daylight vision. More peripheral parts branes of the photoreceptors have to that reptiles and fish are “cold blood- of the retina can detect the slightest be in contact with the eye’s pigment ed” and need to be active in the warm glimmer of photons at night. Most epithelial layer, which provides a daytime. Most mammals have retinas mammals have two types of cones, steady stream of the vital molecule, in which rods predominate. When the green-sensitive and blue-sensitive, but retinal or vitamin A. Retinal becomes number of mammals started to ex- primates have three types—red-sensi- plode as the dinosaurs died out, the tive as well as the other two. With our Helga Kolb is professor emeritus of ophthalmology Earth was likely a dark place covered cone vision, we can see from gray and visual sciences at the University of Utah. She in ash and clouds; the tiny, fur-covered dawn to the dazzling conditions of studied at the University of Bristol, completing her early mammals were able to generate high noon with the sun burning down Ph.D. in 1971. She conducted eye research at the their own body heat and developed on white sand. Initially the cone photo- Institute of Ophthalmology in London, where she visual systems sensitive to dim light. receptors themselves can adapt to the became involved in studies of electrophysiology and Modern rodents such as rats and mice, surrounding brightness, and circuitry anatomy, and later moved to positions at Johns Hopkins and the National Institutes of Health. She which are nocturnal animals, still have through the retina can further modu- joined the Utah faculty in 1979. Address: Univer- retinas overwhelmingly dominated by late the eye’s response. Similarly, the sity of Utah Health Sciences Center, 75 North rods; their cones are small in size and rod photoreceptors and the neural cir- Medical Drive, Salt Lake City, Utah 84132. Inter- only make up 3 to 5 percent of their cuitry to which they connect can adapt net: [email protected] photoreceptors. to lower and lower intensity of light. © 2003 Sigma Xi, The Scientific Research Society. Reproduction with permission only. Contact [email protected]. 28 American Scientist, Volume 91 Figure 1. Intricately wired neurons in the retina allow a good deal of image assembly to take place in the eye itself. The author estimates that sci- entists understand about half of the interactions among the cells in this delicate piece of tissue. In this rendering, light enters the eye from the left. The photons travels through the vitreous fluid of the eyeball and penetrate the entire retina, which is about half a millimeter thick, before reaching the photoreceptors—the cones and rods that respond to light (the colored and black cells attached to the epithelium at right). Signals then pass from the photoreceptors through a series of neural connections toward the surface of the retina, where the ganglion-cell nerve-fiber layer relays the processed information to the optic nerve and into the brain. (Drawing by the author.) Anatomy and Physiology Imaging techniques ranging from old- like those observed in other neurons. Understanding the anatomy of the pri- style Golgi silver staining, first used However, the first recordings of im- mate retina is essential to understand- over a century ago by Ramón y Cajal, pulses within the retina by Gunnar ing its function. Again, the photore- to electron microscopy and modern- Svaetichin in the 1950s showed very ceptors lie in a layer against the back day antibody staining have revealed odd responses to light. Neurons in the of the eyeball. In the second of three the shapes and sizes of the retina’s cell outer retina—it was not immediately cell layers, called the inner nuclear lay- types and how the different cells con- clear which cells he was recording er, lie one to four types of horizontal nect to form synapses. Staining tech- from—responded to stimulation not cells, 11 types of bipolar cells and 22 to niques have revealed electrical junc- with depolarizing spikes but with slow 30 types of amacrine cells. The numbers tions between cells and the identity hyperpolarization. These “S potentials” vary depending on species. The sur- and location of neurotransmitter recep- are now known to originate with the face layer of the retina contains about tors and transporters. We now know photoreceptors and to be transmitted to 20 types of ganglion cells. Impulses that the neurotransmitter (chemical horizontal cells and bipolar cells. The from the ganglion cells travel to the signal) passed through the vertical membrane hyperpolarization starts on brain via more than a million optic pathways of the retina—from photore- exposure to light, follows the time nerve fibers. The spaces separating ceptors to bipolar cells to ganglion course of a light flash and then returns these three layers are also anatomically cells—is glutamate. The horizontal and to the baseline value when the light is distinct. The region containing synaps- amacrine cells send signals using vari- off. This reflects the counterintuitive es linking the photoreceptors with ous excitatory and inhibitory amino fact that both rods and cones release bipolar and horizontal cell dendrites is acids, catecholamines, peptides and ni- neurotransmitters during the dark, known as the outer plexiform layer; the tric oxide. when the membrane is depolarized area where the bipolar and amacrine Electrophysiological investigations and sodium ions flow freely across the cells connect to the ganglion cells is the of the retina started 60 years ago. Stud- photoreceptors’ cell membranes. When inner plexiform layer. ies of the optic nerve fibers showed that exposed to light, ion channels in the Decades of anatomical studies have they could be stimulated to give tradi- cell membranes close. The cells go into shed light on how the retina works. tional depolarizing action potentials, a hyperpolarized state for as long as © 2003 Sigma Xi, The Scientific Research Society. Reproduction with permission only. Contact [email protected]. 2003 January–February 29 cells to respond to photoreceptor input choroid pigment epithelium differently (Figure 7). Some bipolar cells sclera are tuned to faster and some to slower retina fluctuations in the visual signal; some cornea photoreceptors glutamate receptors resensitize rapidly outer plexiform and others more gradually. The cells pupil inner nuclear inner plexiform thus fire either quickly in succession or relatively slowly in response to the ganglion cells same amount of stimulation.