Ординатура / Офтальмология / Английские материалы / The Retina and its Disorders_Besharse, Bok_2011

Figure 11 Pathways underlying the response properties of the local edge detector. This cell responds to subreceptive field detail at its receptive field center, most likely from the bipolar cells that drive it. It also receives local ON and OFF inhibition that is glycinergic (green arrows), as well as broad-field inhibition (green arrows) that is GABAergic and also responsive to fine detail. In this cell type, GABA is only fed back, not fed forward.

vertical glycinergic and lateral GABAergic activity as shown in Figure 11. The role of this neuron in the overall scheme of vision remains obscure, but it is likely involved in high-resolution, slow temporal response activity.

See also: GABA Receptors in the Retina; Information Processing: Amacrine Cells; Information Processing: Bipolar Cells; Information Processing: Contrast Sensitivity; Information Processing: Direction Sensitivity; Information Processing: Ganglion Cells; Information Processing: Retinal Adaptation.

Further Reading

Barlow, H. B. (1953). Summation and inhibition in the frog’s retina.

Journal of Physiology 119: 69–88.

Beaudoin, D. L., Borghuis, B. G., and Demb, J. B. (2007). Cellular basis for contrast gain control over the receptive field center of mammalian retinal ganglion cells. Journal of Neuroscience 27: 2636–2645.

Demb, J. B. (2008). Functional circuitry of visual adaptation in the retina.

Journal of Physiology 586: 4377–4384.

Fried, S. I., Munch, T. A., and Werblin, F. S. (2002). Mechanisms and circuitry underlying directional selectivity in the retina. Nature 420: 411–414.

Fried, S. I., Munch, T. A., and Werblin, F. S. (2005). Directional selectivity is formed at multiple levels by laterally offset inhibition in the rabbit retina. Neuron 46: 117–127.

Hsueh, H. A., Molnar, A., and Werblin, F. S. (2008). Amacrine to amacrine cell inhibition in the rabbit retina. Journal of Neurophysiology 100(4): 2077–2088.

Lee, S. and Zhou, Z. J. (2006). The synaptic mechanism of direction selectivity in distal processes of starburst amacrine cells. Neuron 51: 787–799.

Levick, W. R. (1965). Receptive fields of rabbit retinal ganglion cells.

American Journal of Optometry and Archives of American Academy of Optometry 42: 337–343.

Maturana, H. R., Lettvin, J. Y., McCulloch, W. S., and Pitts, W. H. (1960). Anatomy and physiology of vision in the frog (Rana pipiens).

Journal of General Physiology 43(supplement 6): 129–175. Molnar, A. and Werblin, F. (2007). Inhibitory feedback shapes bipolar

cell responses in the rabbit retina. Journal of Neurophysiology 98: 3423–3435.

Roska, B., Molnar, A., and Werblin, F. S. (2006). Parallel processing in retinal ganglion cells: How integration of space-time patterns of excitation and inhibition form the spiking output. Journal of Neurophysiology 95: 3810–3822.

van Wyk, M., Taylor, W. R., and Vaney, D. I. (2006). Local edge detectors: A substrate for fine spatial vision at low temporal frequencies in rabbit retina. Journal of Neuroscience 26: 13250–13263.

Werblin, F. S. and Dowling, J. E. (1969). Organization of the retina of the mudpuppy, Necturus maculosus. II. Intracellular recording. Journal of Neurophysiology 32: 339–355.

Glossary

Contrast – Magnitude of luminance variation with respect to mean luminance, defined as Weber contrast (Cw) for discrete stimuli: CW ¼ ðIT IBÞ=IB, where I T and IB refer to the retinal illuminance of a test probe and background, respectively; or as Michelson contrast (CM) for periodic stimuli:

CM ¼ ðImax IminÞ=ðImax þ IminÞ, where Imax is the

maximum retinal illuminance and Imin is the minimum retinal illuminance.

Gain – Change in the neural response produced by either a change in luminance or a change in contrast over the range for which the stimulus–response function is reasonably linear, specified in units such as impulses per quantum or impulses per percent contrast.

Luminance – Amount of light given off by an extended source, either emitted or reflected, and usually specified in candelas per square meter (cd m 2), although many alternative units exist, including apostilbs (asb), foot-lamberts (ftL), millilamberts (mL), and nits.

Retinal illuminance – Luminance in cd m 2 multiplied by pupil area in square millimeters (mm2) and specified in trolands (td).

Threshold – In psychophysics, the light level that marks the transition from invisibility to visibility, defined as either the absolute threshold (‘‘yes, I see it’’) or the difference threshold (‘‘yes, it is different’’); in electrophysiology, the light level that elicits a criterion neural response amplitude or a criterion change in response amplitude.

The eye can potentially be exposed to an enormous range of light intensities, ranging from a few photons per second under extremely dim lighting conditions to light levels that can be more than 10-billion-fold higher (i.e., a factor of 1010 or 10 log units). Furthermore, there may be rapid temporal fluctuations in the light level due to eye movements. In addition, there can be marked changes in the chromatic properties of the visual environment, such as when viewing objects in incandescent room illumination versus outdoors at noon on a sunny day. Remarkably, the visual system is able to cope with the large range of illumination conditions through complex neural mechanisms that are collectively termed adaptation.

It should be noted, however, that there are actually a number of different uses of the term adaptation, ranging from an adjustment to the overall light level to more complex forms, such as spatial frequency adaptation, motion adaptation, and adaptation to artificially induced retinal image distortion or rotation. The emphasis of this article is on adaptation that is presumed to occur within the retina. How do we know which processes are retinal and which involve higher levels of the visual system? One method is to identify neurons within the retina that exhibit the physiological characteristics of the type of adaptation under investigation. This can be determined by recording from single neurons within the retina, by recording simultaneously from groups of neurons using a multi-electrode array, or by recording the electroretinogram (ERG), which is the massed electrical response of the retina. Further insight into the sites and mechanisms of adaptation can be gained through the study of transgenic animals that have a mutation in, or knockout of, putative components of the adaptation process, or of humans who have spontaneously occurring mutations in these components.

A complementary, behavioral method for investigating the site of adaptation is to employ dichoptic stimulation. In this technique, an adapting stimulus is presented to one eye and a test stimulus is presented to the other eye. The goal is to determine whether adaptation of the contralateral eye affects performance for targets presented to the tested eye. The first site at which there is a combination of information from the two eyes occurs at a cortical level. Therefore, if there is interocular transfer of the adaptation, then it is presumed that the primary site of the adaptation is cortical. On the other hand, if there is no evidence of interocular transfer, then the adaptation is presumed to occur at the retinal level.

Based on such considerations, the forms of adaptation that are thought to be predominantly or exclusively retinal in origin are: (1) light adaptation, which refers to the adjustment of the visual system to changes in the overall or mean illumination level; (2) contrast adaptation, which refers to the ability of the visual system to adjust to the variance of the illumination rather than to its mean; (3) chromatic adaptation, which refers to an adjustment to the spectral composition of light; and (4) dark adaptation, which refers to the time-dependent recovery of visual sensitivity in the dark following exposure to light. These forms of adaptation are the subject of this article, although the emphasis is on light adaptation.

326 Information Processing: Retinal Adaptation

In addition to adaptation, though, there are additional strategies that are employed by the visual system to cope with the broad range of illumination levels encountered by the visual system. One strategy is a change in pupil size, which is a mechanical way in which the visual system can partially adjust to varying light levels. As the overall light level increases, the pupil area decreases, which in turn decreases the retinal illuminance. However, the maximum change in pupil area is essentially 16-fold (i.e., a change in diameter from 2 to 8 mm); therefore a change in pupil size can compensate for only a small portion of the potential illumination range. Furthermore, owing to the directional sensitivity of the cone photoreceptors (the Stiles–Crawford effect), light entering the edge of the pupil is a less efficient stimulus for the cone system than light entering the pupil center. Therefore, the effective increase in retinal illuminance with increasing pupil size is actually less than would be predicted based on pupil area.

Another strategy used by the visual system to cope with the large range of environmental light levels is to split the load between the rod and cone systems. The rod system, which is extremely sensitive, covers the lower 3 log units of stimulation, termed the scotopic range. The cone system handles the highest 6 log units, termed the photopic range. Between these two ranges is the mesopic range, within which visual sensitivity can be rod-mediated or cone-mediated, depending on such factors as target wavelength, duration, size, and retinal eccentricity. Thus, the duplex nature of the retina provides a partial solution to the problem of dealing with the wide range of light levels impinging on the retina. However, adaptive processes within the rod and cone systems are also necessary in order to provide useful vision under all illumination conditions.

Light Adaptation

Light adaptation typically refers to the adjustment of the visual system to the overall illumination level. This adjustment allows for an amplification of neural signals relative to noise at low light levels, and prevents or minimizes saturation of the neural response at high light levels. Light adaptation also changes the way in which spatial and temporal information is processed. For example, spatial resolution is typically better at high illumination levels.

Characteristics of Light Adaptation

The typical light adaptation paradigm consists of the presentation of a brief test probe of retinal illuminance IT against an adapting field of retinal illuminance IB.

law is that the visual system is organized to signal contrast rather than absolute luminance. In other words, becauseI =IB is constant within the Weber region, Weber contrast is also constant, regardless of the adapting level.

The data of Figure 1 represent a tvi function for the foveal cone system, but an increment threshold function can also be obtained for the rod system if a short-wavelength test probe, to which the rods are sensitive, is presented in the visual field periphery against a long-wavelength adapting field that desensitizes the cone system. A schematic of a rod increment threshold function is shown in Figure 2. As is the case for the cone system, there is a range of low retinal illuminances over which the rod threshold remains constant. This is followed by a region over which the rod threshold is proportional to the square root of the retinal illuminance (the Rose–deVries region), and then there is a transition to Weber-law behavior. However, a primary difference between the rod and cone increment threshold functions is that the rod function shows saturation, or an upward turn at high retinal illuminances that is steeper than Weber’s law. For adapting field retinal illuminances above rod saturation, the cone system mediates detection of the test probe.

Saturation can be observed in individual rod photoreceptors, in the sense that there can be a complete shutdown of the rod circulating current resulting from light exposure. However, there is considerable evidence that psychophysical rod saturation does not represent saturation at the level of the rod photoreceptors, but rather is a property of the pathway through which the

log IB(scot td)

Figure 2 Schematic increment threshold function obtained under rod-isolating conditions. The inset depicts the stimulus configuration, which consists of a large short-wavelength (blue) test probe presented in the visual field periphery against a larger long-wavelength (red) adapting field.

rod signals travel. For example, the value of IB at which the onset of psychophysical rod saturation occurs depends on whether the adapting field is steady or flashed, on the size of the test probe and the wavelength of the adapting field, and on the level of cone stimulation, all of which indicate that postreceptoral factors are involved.

The tvi function of the cone system typically does not show saturation, owing to photopigment bleaching. When cone photopigment molecules become bleached as a result of light exposure, there is less total photopigment within a cone photoreceptor that is available to capture photons. As a result, a proportionally greater level of stimulation is needed to produce the same neural response. At equilibrium, the relationship between p, the fraction of unbleached cone photopigment, and retinal illuminance I in td is:

where I0 is the half-bleaching constant of 4.3 log td. The effect of cone photopigment bleaching on vision has been likened to wearing sunglasses, which reduce the retinal illumination by a scaling factor. Photopigment bleaching is a way of avoiding saturation within the cone system but it is not a factor within the rod system, because the rod photoreceptors are saturated by illumination levels that bleach only a few percent of the rhodopsin molecules within an outer segment.

However, saturation within the cone system can be demonstrated if a probe-flash paradigm is used. In this paradigm, the test probe is presented simultaneously with a briefly flashed adapting field. A typical finding is that the threshold rises rapidly with increasing retinal illuminance of the flashed adapting field, such that at high retinal illuminances, the test probe itself is invisible and its presence can only be detected by virtue of an afterimage.

The probe-flash paradigm is a variant of Crawford masking or early light adaptation, in which the increment threshold for a test probe is measured with respect to the time of onset of a transient rather than a steady-state adapting field. Typically, the threshold begins to rise when the test probe is presented slightly before the masking flash. This curious result has been attributed to the differential latencies of the neural responses to the weak test probe and the stronger masking flash. The threshold is highest when the test probe and masking flash have simultaneous onsets. If the test probe is presented during the middle of a long-duration masking flash, then the threshold corresponds approximately to the steady-state level.

Traditionally, studies of light adaptation have used aperiodic test stimuli, such as the light pulses described above. However, there has been another experimental approach to light adaptation that has used periodic test stimuli, such as one whose retinal illuminance varies sinusoidally over time. In this approach, the dependent variable is contrast sensitivity, defined as the reciprocal of

the threshold contrast in Michelson units. A typical finding is that, at low temporal frequencies, contrast sensitivity is invariant with respect to mean retinal illuminance, which corresponds to Weber-law behavior. At high temporal frequencies, however, contrast sensitivity changes with mean retinal illuminance, such that the amplitude of the flicker rather than its contrast determines sensitivity. This finding indicates that there is a high-frequency linearity that discounts the mean retinal illuminance. In addition, the shape of the temporal contrast sensitivity function changes with adaptation level, becoming more band-pass at high retinal illuminances, so that sensitivity to intermediate frequencies becomes enhanced. This shape change has been attributed to a contrast gain-control mechanism.

The explanation for the high-frequency linearity, which is seen both psychophysically and in electrophysiological recordings, remains unclear, although several quantitative models have been proposed to account for it. In fact, a major theoretical challenge has been to develop a computational model that can encompass the adaptational features of data obtained with both periodic and aperiodic stimuli. To date, this attempt has not been entirely successful.

Mechanisms and Sites of Light Adaptation

As illustrated in Figures 1 and 2, the rod and cone systems can respond over a considerable range of retinal illuminances. However, individual neurons within the retina can only respond over an approximately 400-fold range of illumination levels. The typical response R of a retinal neuron as a function of retinal illuminance I is illustrated as the solid curve in Figure 3. This curve represents a plot of the Naka-Rushton equation:

where Rmax is the maximum neural response, Is is the retinal illuminance that produces Rmax=2, and n governs the steepness of the function, although n is usually set to 1. This response function is S-shaped when plotted on semilog coordinates, as in Figure 3. A major characteristic of the neural response function is that it shows saturation at high illuminance levels. The response function is considered to represent a static nonlinearity, or one which acts instantaneously with no change over time.

If a retinal neuron only operated according to the solid curve in Figure 3, then the presence of an adapting field would lead to response compression. For example, the adapting field indicated by the vertical line in Figure 3 would produce a neural response that is toward the top of the response range, as indicated by the solid horizontal line. This would then leave little room for an additional response to an increment of light. In fact, if the retinal illuminance of the adapting field were high enough,

Figure 3 Normalized response amplitude vs. log retinal illuminance for a hypothetical retinal neuron before (solid curve) and after (dashed curve) a multiplicative transform. The vertical line with arrowhead indicates an arbitrary adapting field retinal illuminance, and the horizontal lines represent the hypothetical neural responses to the adapting field, based on the respective illuminance-response functions.

additional increments of light would be invisible due to response saturation.

One way in which a neuron can avoid saturation is by shifting its operating range in proportion to the mean level of illumination. This shift of the response function is termed multiplicative adaptation and is illustrated in Figure 3 as the dashed curve. Multiplicative adaptation is also known as von Kries adaptation, dark glasses adaptation, and automatic gain control. After a multiplicative transform, the same adapting field retinal illuminance produces a smaller neural response, as indicated by the horizontal dashed line in Figure 3. This allows for the detection of light increments that would otherwise be invisible without the multiplicative response scaling. Multiplicative adaptation tends to be relatively fast acting, with a time constant on the order of a few tens of milliseconds, and is thought to be the result of a neural feedback circuit.

A second way in which a neuron can avoid saturation is through subtractive adaptation. This form of adaptation subtracts out the neural response to an adapting field, thus bringing the response down out of the saturating range, without affecting the response to a brief test probe. There are both fast and slow forms of subtractive adaptation, although both are typically much slower than multiplicative adaptation, with time constants on the order of seconds to tens of seconds. Fast subtractive adaptation is presumed to represent center-surround antagonism within neuronal receptive fields. Slow subtractive adaptation may be due to a change in the membrane hyperpolarization of retinal neurons.

The rod system is desensitized by dim backgrounds that produce a quantal absorption in only a very few rod photoreceptors. This observation has led to the concept of a rod adaptation pool, according to which signals from

multiple rod photoreceptors are combined in controlling light adaptation. Pooling allows a retinal ganglion cell to respond to light when only a tiny fraction of the rods absorb photons, but it also increases the likelihood of neuronal saturation. Neural pooling can also be a factor with respect to light adaptation within the cone system. Signals from cone photoreceptors are processed by two major parallel pathways: magnocellular (M) and parvocellular (P), which are first organized at the retinal level and extend to the visual cortex. M retinal ganglion cells have a high contrast gain and saturate at relatively low levels of contrast. P ganglion cells have a low contrast gain and a more linear contrast-response function. There is generally a greater degree of spatial integration or pooling within M cells, due to their relatively larger receptive fields. Therefore, M cells are typically more light adapted by a given adapting field than are P cells.

The retinal site or sites of the various neural processes underlying light adaptation remain to be fully explicated. However, the following general conclusions can be drawn. With respect to the cone system, the site of adaptation appears to shift depending on the illumination level. At lower retinal illuminances, adaptation is dominated by postreceptoral processes, sometimes referred to as network adaptation. There is recent evidence that postreceptoral adaptation within the cone system occurs at the synapse between bipolar cells and ganglion cells. At higher retinal illuminances, adaptation occurs primarily within the cone photoreceptors themselves. Rod photoreceptors in the mammalian retina can show adaptation, in that there are changes in sensitivity and response kinetics as a function of illumination level. However, much of the light adaptation within the rod system appears to be postreceptoral in origin, occurring at the synapse between rod bipolar cells and AII amacrine cells.

A potentially powerful way to investigate the relationship between the phenomenology of light adaptation and retinal physiology is to study humans who have genetic mutations that can affect putative components of the adaptational process. An example is a visual condition termed bradyopsia (slow vision) that has been identified recently. Individuals with bradyopsia have mutations in the guanosine triphosphatase-activating protein RGS9 or its anchor protein R9AP, which impedes deactivation of the phototransduction cascade. Bradyopsia is characterized by a slow recovery of sensitivity following a sudden change in illumination and also a loss of motion sensitivity, particularly at low contrasts.

Contrast Adaptation

Contrast adaptation refers to an adjustment to the variance or contrast of the illumination, rather than to its mean level. There are two types of contrast adaptation:

spatial and temporal. Spatial contrast adaptation is selective for stimulus spatial frequency and orientation and is therefore predominantly cortical in origin. Temporal contrast adaptation, on the other hand, is observed in recordings from retinal ganglion cells in response to spatially uniform fields of light. Examples of stimuli used to study contrast adaptation are illustrated in Figure 4. Both involve the temporal modulation of a uniform field of light. One type of stimulus (Figure 4, top) is contrast-modulated sinusoidal flicker, whose mean luminance and temporal frequency remain constant but whose contrast is changed abruptly. The second (Figure 4, bottom) is contrast-modulated white noise.

Following a transition from a low-contrast to a highcontrast stimulus, there is an essentially instantaneous change in the gain and temporal response of retinal ganglion cells. This is followed by a slow change in the firing rate that may take several seconds to complete. There are similar fast and slow changes following a transition from a high-contrast to a low-contrast stimulus, including a temporary decrease in the maintained discharge rate, but these changes are typically more sluggish than for a transition to high contrast. Fast contrast adaptation represents the action of a gain-control mechanism, whereas slow contrast adaptation appears to involve membrane hyperpolarization. Temporal contrast adaptation may form the neural substrate for psychophysical flicker adaptation, in which exposure to high-contrast flicker reduces sensitivity for a subsequently viewed low-contrast flickering test stimulus.

Temporal contrast adaptation has been shown to occur at multiple sites within the retina, beginning in bipolar cells and including processes intrinsic to ganglion cells.

0

Time (ms)

Figure 4 Examples of contrast-modulated stimuli used to study contrast adaptation. The top waveform is a contrastmodulated sinusoid; the bottom waveform represents contrastmodulated noise.

Temporal contrast adaptation is observed in M but not in P ganglion cells, owing in part to the faster temporal response and greater spatial pooling of M cells. Contrast adaptation and mean-luminance adaptation share certain similarities, but whether these forms of adaptation represent a common mechanism or distinct mechanisms remains to be determined.

Chromatic Adaptation

Chromatic adaptation refers to the effect of spectrally selective adapting fields on the detection and appearance of test stimuli of various wavelengths. When chromatic test probes and adapting fields are used to study light adaptation, the increment threshold function of the foveal cone system typically consists of more than one component, as illustrated in Figure 5. With the combination of test and adapting field wavelengths shown in Figure 5, the test probe is initially detected by a middle-wavelength-sensitive mechanism that becomes progressively more desensitized by the middle-wavelength adapting field. At high retinal illuminances, a short-wavelength-sensitive cone mechanism governs detection.

A change in test wavelength displaces a given tvi function vertically, and a change in adapting field wavelength displaces the tvi function horizontally. Initially, it was thought that the spectral sensitivities of the short-wavelength (S), middle-wavelength (M), and long-wavelength (L) cone photopigments could be derived by evaluating the relative displacements of the tvi functions as the test wavelength and

Figure 5 Schematic tvi functions for a 475-nm test probe (blue) presented foveally against a 550-nm adapting field (green), plotted in relative units. The curves represent plots of the tvi template of Stiles, and the lower (green) and upper (blue) branches represent detection by middle-wavelength-sensitive and short-wavelength-sensitive cone mechanisms, respectively.

adapting field wavelength were varied. This approach was used by W. S. Stiles to define what are known as p mechanisms. However, instead of identifying three p mechanisms corresponding to the three cone types, seven p mechanisms were derived from this method. The field sensitivities of three of the seven (p1, p4, and p5) correspond approximately to the spectral sensitivities of the S, M, and L cones, respectively. Nevertheless, the shapes of the p4 and p5 mechanisms are broader than would be expected from the known spectra of the cone photopigments, and there are other failures of the p mechanisms to correspond to properties predicted by adaptation of the cone photoreceptors.

Partly to account for the mismatch between the properties of the p mechanisms and the cone spectral sensitivities, two-stage models of chromatic adaptation have been developed. The first stage consists of receptor adaptation, and the second stage combines signals from the S, M, and L cones in an opponent manner. The site of the opponent interactions among signals from different cone types has not yet been identified definitively. Candidates include horizontal cells (although these are not typically spectrally opponent), amacrine cells, and possibly gap-junctional connections between photoreceptors.

Chromatic adaptation also refers to a change in the color appearance of a test light as a result of a change in adapting field chromaticity. For example, a monochromatic light that appears yellow in isolation will appear greenish when superimposed on a long-wavelength adapting field. This change in color appearance has been attributed to a relative desensitization of the L-cone photoreceptors through von Kries or multiplicative adaptation. However, there are instances in which photoreceptor desensitization alone cannot account for the changes in color appearance, such as when the level of retinal illuminance is changed, or when a monochromatic light becomes desaturated during extended viewing. These changes in color appearance are presumably due to second-site adaptation in addition to cone photoreceptor adaptation. Two-stage models are also presumed to account for color constancy, in which colored surfaces maintain their appearance despite substantial changes in the spectral content of the illumination, such as the change from sunlight to incandescent lighting.

Dark Adaptation

Following the exposure of the eye to an adapting field that bleaches a significant fraction of photopigment, there is a systematic recovery of visual sensitivity that is referred to as dark adaptation. Whereas light adaptation occurs relatively quickly, dark adaptation can require a substantial period of time, on the order of tens of minutes. Strictly speaking, the term dark adaptation refers to the recovery of sensitivity to a briefly flashed test probe presented in complete darkness following the offset of a bleaching

light. However, there are also variants of bleaching recovery in which the eye is not kept in darkness. These include the photostress recovery test, which measures the recovery of visual acuity following exposure to light from an ophthalmic instrument.

Characteristics of Dark Adaptation

The typical time course of dark adaptation following a bleach is illustrated in Figure 6. The data points in this figure represent thresholds for a test probe of 500 nm, a wavelength to which rod and cone systems are both sensitive. The test probe was presented at a retinal eccentricity of 20 , a retinal locus that contains both rod and cone photoreceptors. Thresholds are plotted relative to a baseline threshold that was measured in the fully dark-adapted state prior to a bleach. The recovery of sensitivity follows a two-branched course, each part of which is reasonably well fit by an exponential function. Immediately following the offset of the bleaching light, the recovery of sensitivity occurs relatively rapidly, and then sensitivity reaches a plateau region. This initial portion represents the recovery of cone system sensitivity. There is then a second region of rapid recovery followed by a slower phase, such that full recovery from a substantial bleach can take 45–50 min. This second region represents the return of rod system sensitivity. The transition point from cone-mediated to rod-mediated thresholds is termed the rod–cone break.

Time (min)

Figure 6 Recovery of visual sensitivity following exposure to a bleaching light, measured with a test probe of 500 nm presented to the peripheral retina in the dark. Thresholds are plotted with respect to the prebleach dark-adapted threshold. The dashed and solid curves are exponential functions fit to the conemediated (upper) and rod-mediated (lower) portions of the dark adaptation data, respectively.

Although the rod portion of the dark adaptation function in Figure 6 has been fit with an exponential function, it is more accurately represented by several regions with linear slopes on log-linear coordinates, with each region representing a different physiological process.

The relative vertical placements of the rod and cone dark adaptation curves and the time course of the recovery of sensitivity depend on a number of factors, including the retinal location of testing, the wavelength of the test probe, and the retinal illuminance of the bleaching light. For example, dark adaptation testing at the rodfree fovea reflects only the cone portion of the curve. Long-wavelength test probes, to which the rod system is relatively insensitive, typically produce a less-pronounced and delayed rod–cone break. Weak bleaching lights produce a faster time course of recovery than strong bleaches.

The psychophysical threshold not only is elevated following the offset of a bleaching light, but it is also elevated by the presence of an adapting field. This correspondence has led to the concept of the equivalent background, which holds that the aftereffect of a bleach is equivalent to the presence of a background of real light. This equivalent background, which is sometimes termed dark light, is generally not visible because it is stabilized on the retina. However, it can sometimes be observed in the form of an afterimage. Real light and dark light may have similar properties under some test conditions, but they are not always identical.

Although dark adaptation typically follows the time course illustrated in Figure 6, it is not always the case that sensitivity improves following the offset of a bleaching light. Under certain conditions, sensitivity actually decreases as dark adaptation progresses. One example occurs when the task is to determine the hue threshold or Lie specific threshold, which refers to the retinal illuminance of a test probe at which it appears to have a color. The hue threshold begins to rise at the time of the rod– cone break, rather than remaining constant once the cones have recovered. This rise in the threshold for hue has been attributed to an influence of the recovering rod system on color appearance.

A second example occurs when the task is to determine whether a rapidly flickering test stimulus, presented at a frequency above the rod temporal resolution limit, appears to flicker. The threshold for flicker detection does not remain constant once the cone system has recovered, but instead rises as the rods recover their sensitivity. The rise in the flicker threshold has been attributed to a suppressive effect of the dark-adapting rod system that surrounds the test stimulus on the temporal sensitivity of the cone system.

A threshold elevation during dark adaptation also occurs when the task is to detect a short-wavelength test probe following the offset of a long-wavelength adapting field. In this case, there is a substantial threshold elevation immediately following the adapting field offset, which is

followed by a gradual decrease in threshold. The brief threshold increase, termed transient tritanopia, is thought to represent a change in sensitivity within a postreceptoral opponent color mechanism. Transient tritanopia can also be observed in the ERG, indicating that it is retinal in origin.

Mechanisms of Dark Adaptation

The recovery of sensitivity in the dark, following light exposure, depends ultimately on the regeneration of bleached photopigment. For example, individuals with vitamin A deficiency, which limits the regeneration of rod photopigment, typically have a prolonged time course of rod dark adaptation, and rod thresholds may never reach a normal level. Yet, the recovery of rod sensitivity depends on more than the regeneration of a light absorber. This is demonstrated by the fact that rod thresholds remain elevated by 2 to 4 log units at a time when 90% of rhodopsin has been regenerated following a bleach. It is likely that the presence of various bleaching intermediates, such as metarhodopsin products and free opsin, contribute to the rod threshold elevation during dark adaptation.

In addition to physiological processes occurring within photoreceptors, it is apparent that postreceptoral factors are involved in the recovery of sensitivity during dark adaptation. For example, a change in the size of the test probe can influence the shape of the dark-adaptation curve, although test probe size should have no influence on the rate of photopigment regeneration. Furthermore, dim lights that bleach a trivial amount of photopigment and that have no effect on the receptor potential or on horizontal cell responses in the skate retina, nevertheless, result in an elevation of ERG b-wave and ganglion cell thresholds that requires several minutes to recover. Thus, dark adaptation appears to involve mechanisms at multiple levels within the retina.

Human gene mutations are continuing to provide important insights into the physiological processes underlying dark adaptation. For example, mutations in either the rhodopsin kinase gene or the arrestin gene produce Oguchi disease, in which there is a prolonged recovery of rod sensitivity following light exposure that is thought to be due to impaired deactivation of rhodopsin. Mutations in the RDH5 gene, which encodes the enzyme 11-cis retinol dehydrogenase, result in fundus albipunctatus, which is characterized by extremely prolonged rod dark adaptation, presumably due to an impairment in the conversion of 11-cis retinol to 11-cis retinal.

Conclusion

stimulation. Through the use of psychophysical and electrophysiological techniques, great progress has been made in understanding the fundamental mechanisms underlying retinal adaptation, but many of the details have yet to be clarified. Studies of transgenic animal models and of naturally occurring human mutations, in which there are alterations in the putative components of adaptation, show great promise in furthering our knowledge of this fundamental visual process.

See also: Anatomically Separate Rod and Cone Signaling Pathways; Information Processing: Contrast Sensitivity; Perimetry; Photopic, Mesopic and Scotopic Vision and Changes in Visual Performance; Phototransduction: Adaptation in Cones; Phototransduction: Adaptation in Rods; Unique Specializations – Functional: Dynamic Range of Vision Systems.

Further Reading

Demb, J. B. (2008). Functional circuitry of visual adaptation in the retina.

Journal of Physiology 586: 4377–4384.

Dowling, J. E. (1987). The Retina: An Approachable Part of the Brain.

Cambridge: Belknap Press.

Dunn, F. A., Doan, T., Sampath, A. P., and Rieke, F. (2006). Controlling the gain of rod-mediated signals in the mammalian retina. The Journal of Neuroscience 26: 3959–3970.

Dunn, F. A., Lankheet, M. J., and Rieke, F. (2007). Light adaptation in cone vision involves switching between receptor and post-receptor sites. Nature 449: 603–606.

Graham, N. and Hood, D. C. (1992). Modeling the dynamics of light adaptation: The merging of two traditions. Vision Research 32: 1373–1393.

Hess, R. F., Sharpe, L. T., and Nordby, K. (eds.) (1990). Night Vision: Basic, Clinical and Applied Aspects. New York: Cambridge University Press.

Hood, D. C. (1998). Lower-level visual processing and models of light adaptation. Annual Review of Psychology 49: 503–535.

Kaplan, E., Lee, B. B., and Shapley, R. M. (1990). New views of primate retinal function. In Osborne, N. N. and Chader, G. T. (eds.) Progress in Retinal Research, vol. 9, pp. 273–336. Oxford: Pergamon Press.

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Relevant Websites

Retinal adaptation refers to diverse visual phenomena and neural processes, all of which represent the adjustment of the visual system to the prevailing conditions of light

http://webvision.med.utah.edu – Webvision: Light and Dark Adaptation.

http://cvision.ucsd.edu – CVRL Color and Vision database.

Glossary

Cecocentral scotoma – Visual field defect involving the optic disk area (blind spot) and papillomacular bundle (PMB) fibers.

Cybrid cells – These are a eukaryotic cell line produced by the fusion of a whole cell with a cytoplasmic mitochondria.

Donder’s curve – An expected reduction of lenticular accommodation as a function of age. Dyschromatopsia – A partial or complete loss of color vision.

Genetic penetrance – The degree to which individuals express a genetically determined condition.

Papillomacular fibers – Axons from the smaller retinal ganglion cells that carry the information from the macula.

Searching nystagmus – A condition where

both eyes occasionally make a wide, comparatively slow, sweeping movement caused by poor vision. Tapetoretinal – The region of the photoreceptors and retinal pigment epithelium in the retina.

Inherited optic neuropathies fall under the rubric of metabolic optic neuropathies. Metabolic optic neuropathies share many pathophysiologic and clinical characteristics. Most metabolic optic neuropathies involve derangements that affect mitochondria and oxidative phosphorylation. Acquired metabolic optic neuropathies are further divided into those of toxic and those of nutritional deficiency states. For example, both ethambutol toxicity and vitamin B12 deficiency produce bilateral symmetrical optic neuropathies that are very similar to inherited optic neuropathies.

This article discusses hereditary optic nerve diseases that affect the optic nerve in isolation. Common hereditary optic neuropathies include Leber’s hereditary optic neuropathy (LHON), dominant optic atrophy (DOA), and congenital recessive optic atrophy (ROA). Like most acquired optic neuropathies, inherited optic neuropathies involve mitochondrial function. In all cases, mitochondria are impaired either by mutations of their own DNA (mtDNA), or mutations of nuclear DNA involved in the transcription of mitochondrial proteins or substrates for mitochondrial biochemistry. All three have a similar presentation inherited mitochondria optic neuropathy.

This makes the diagnosis both challenging and, at the same time, the clinical evaluation similar. The presentation is usually that of bilateral symmetric visual loss with dyschromatopsia, and central or cecocentral visual field defects, which involves the optic disk and papillomacular fibers. This archetypical set of clinical signs reflects the fact that in metabolic optic neuropathies there is a strong predilection for the papillomacular bundle (PMB). The distinctions between acquired and inherited optic neuropathies usually come down to issues of personal history, such as toxic exposure, decreased vitamin intake or malabsorption, and, especially for inherited optic neuropathies, family history. However, because of variable penetrance, the family history in inherited optic neuropathies may not be always positive. Prompt recognition of the characteristic elements from history and physical examinations often precludes unnecessary patient laboratory evaluation.

Leber’s Hereditary Optic Neuropathy

LHON was first described in 1871 by Theodore Leber. Later von Hippel, Gowers, and Collins refined our understanding and introduced the term hereditary optic atrophy. As recently as the 1980s, LHON was considered to be a non-Mendelian inherited genetic disorder, since there was no male-to-male transmission. In 1988, Douglas Wallace demonstrated LHON as the first maternally inherited disease to be associated with point mutations in mitochondrial DNA, and it is now considered the most prevalent mitochondrial disorder.

LHON typically manifests as a subacute central loss of vision that predominantly affects young adult males. Age of onset is usually between 15 and 35 years; however, it has been reported to occur as young as 2 and as old as 80 years of age. Almost invariably the second eye is affected, within weeks to months. LHON is usually due to one of three pathogenic mitochondrial DNA (mtDNA) point mutations. These mutations affect nucleotide positions 11778, 3460, and 14484, respectively, in the ND4, ND1, and ND6 subunit genes of complex I which is integral for oxidative phosphorylation in mitochondria. These three primary mutations are responsible for about 95% of LHON cases; other rarer mutations continue to be described. In some pedigrees of LHON, associated systemic features have been reported; these include cardiac abnormalities such as pre-excitation syndromes and