Photoreceptor Adaptation Research Articles

Macular Edema - Rationale for Therapy.

Macular edema represents the end-stage of multiple pathophysiological pathways in a multitude of ocular vascular, inflammatory, and other diseases. The rationale for clinical treatment of macular edema is based on the understanding and the inhibition of these pathophysiological mechanisms. When macular edema is caused by a generalized health problem such as diabetes, high blood pressure, or generalized inflammatory conditions, treatment of these generalized diseases can in many cases cure macular edema directly. In ocular diseases, the local exudation of fluid from blood vessels is governed by Starling's law as well as by intricate cellular mechanisms linked to the tight junctions in the inner and outer blood-retinal barrier. Drugs used in clinical practice, such as nonsteroidal anti-inflammatory drugs, corticosteroids, carbonic anhydrase inhibitors, and anti-vascular endothelial growth factor agents, all act in one way or another through these cellular mechanisms. Novel treatments such as neuroprotective agents like nerve growth factors, somatostatins and antiapoptotic agents like calpain, the glutamate blocker memantine, and different caspase inhibitors may in the future inhibit neuronal cell death in the retina by separate pathways. Using dimmed nocturnal illumination may be an additional novel method to reduce hypoxic stress during dark adaptation of the rod photoreceptors in diabetes. Successful surgical treatment of macular edema using vitrectomy and peeling relies, apart from the evident release of vitreomacular traction, on many other cellular and biochemical mechanisms activated by the surgery such as oxygenation of the inner retina, removal of the posterior hyaloid as a growth factor sink, and possible Müller cell remodeling with fluid redirection after internal limiting membrane peeling.

Peripheral Processing Facilitates Optic Flow-Based Depth Perception.

Flying insects, such as flies or bees, rely on consistent information regarding the depth structure of the environment when performing their flight maneuvers in cluttered natural environments. These behaviors include avoiding collisions, approaching targets or spatial navigation. Insects are thought to obtain depth information visually from the retinal image displacements (“optic flow”) during translational ego-motion. Optic flow in the insect visual system is processed by a mechanism that can be modeled by correlation-type elementary motion detectors (EMDs). However, it is still an open question how spatial information can be extracted reliably from the responses of the highly contrast- and pattern-dependent EMD responses, especially if the vast range of light intensities encountered in natural environments is taken into account. This question will be addressed here by systematically modeling the peripheral visual system of flies, including various adaptive mechanisms. Different model variants of the peripheral visual system were stimulated with image sequences that mimic the panoramic visual input during translational ego-motion in various natural environments, and the resulting peripheral signals were fed into an array of EMDs. We characterized the influence of each peripheral computational unit on the representation of spatial information in the EMD responses. Our model simulations reveal that information about the overall light level needs to be eliminated from the EMD input as is accomplished under light-adapted conditions in the insect peripheral visual system. The response characteristics of large monopolar cells (LMCs) resemble that of a band-pass filter, which reduces the contrast dependency of EMDs strongly, effectively enhancing the representation of the nearness of objects and, especially, of their contours. We furthermore show that local brightness adaptation of photoreceptors allows for spatial vision under a wide range of dynamic light conditions.

Active control of the visual field in the starfish Acanthaster planci

Photoreception in echinoderms has been studied for several years with a focus on the dermal photoreceptors of echinoids. Even though spatial vision has been proposed for this dermal photosystem, by far the most advanced system is found in a number of asteroids where an unpaired tube foot at the tip of each arm carries a proper eye, also known as the optical cushion. The eyes resemble compound eyes, except for the lack of true optics, and they typically have between 50 and 250 ommatidia each. These eyes have been known for two centuries but no visually guided behaviors were known in starfish until recently when it was shown that both Linckia laevigata and Acanthaster planci navigate their coral reef habitat using vision. Here we investigate the visual system of A. planci and find that they have active control of their visual field. The distalmost tube foot holding the eye is situated on a movable knob, which bends to adjust the vertical angle of the visual field. On the leading arms the visual field is directed 33° above the horizon, whereas the eyes on the trailing arms are directed 44° above horizontal on average. When the animal traverses an obstacle the knob bends and counteracts most of the arm bending. Further, we examined a previously described behavior, rhythmic arm elevation, and suggest that it allows the animal to scan the surroundings while preventing photoreceptor adaptation and optimizing image contrast.

Behavioural response of winged aphids to visual contrasts in the field

To test the behavioural response of winged aphid spring migrants to visual contrasts, we conducted a field trial in which water traps (painted in seven different shades of green and yellow) were set up on uncovered soil and on coloured boards (also painted in seven different colours including black, brown and various shades of green). In total, 56 trap–background combinations were tested. Out of the 4904 aphid individuals caught, 64.5% belonged to Aphis ssp. Using spectral measurements of both traps and backgrounds, as well as information on insect spectral sensitivity, an empirical colour choice model was built based on photoreceptor adaptation to the background, and colour opponency of the green and blue photoreceptor. Specifically, the visual input variable C* represents the difference between green–blue colour opponency values of the trap and the background. When C* > 0, the number of aphids linearly increased with C*. The model explained 64% of the behavioural response of the aphids. Applied to intercropping scenarios of sugar beet, the behavioural model showed a higher visual attractivity of a monocrop sugar beet than intercropped sugar beet. Implications for the use of mulches and for increasing plant diversity in cropping systems are discussed.

Circadian and light-driven regulation of rod dark adaptation.

Continuous visual perception and the dark adaptation of vertebrate photoreceptors after bright light exposure require recycling of their visual chromophore through a series of reactions in the retinal pigmented epithelium (RPE visual cycle). Light-driven chromophore consumption by photoreceptors is greater in daytime vs. nighttime, suggesting that correspondingly higher activity of the visual cycle may be required. However, as rod photoreceptors are saturated in bright light, the continuous turnover of their chromophore by the visual cycle throughout the day would not contribute to vision. Whether the recycling of chromophore that drives rod dark adaptation is regulated by the circadian clock and light exposure is unknown. Here, we demonstrate that mouse rod dark adaptation is slower during the day or after light pre-exposure. This surprising daytime suppression of the RPE visual cycle was accompanied by light-driven reduction in expression of Rpe65, a key enzyme of the RPE visual cycle. Notably, only rods in melatonin-proficient mice were affected by this daily visual cycle modulation. Our results demonstrate that the circadian clock and light exposure regulate the recycling of chromophore in the RPE visual cycle. This daily melatonin-driven modulation of rod dark adaptation could potentially protect the retina from light-induced damage during the day.

Unexpectedly low UV-sensitivity in a bird, the budgerigar.

Photoreceptor adaptation ensures appropriate visual responses during changing light conditions and contributes to colour constancy. We used behavioural tests to compare UV-sensitivity of budgerigars after adaptation to UV-rich and UV-poor backgrounds. In the latter case, we found lower UV-sensitivity than expected, which could be the result of photon-shot noise corrupting cone signal robustness or nonlinear background adaptation. We suggest that nonlinear adaptation may be necessary for allowing cones to discriminate UV-rich signals, such as bird plumage colours, against UV-poor natural backgrounds.

Low aqueous solubility of 11-cis-retinal limits the rate of pigment formation and dark adaptation in salamander rods

We report experiments designed to test the hypothesis that the aqueous solubility of 11-cis-retinoids plays a significant role in the rate of visual pigment regeneration. Therefore, we have compared the aqueous solubility and the partition coefficients in photoreceptor membranes of native 11-cis-retinal and an analogue retinoid, 11-cis 4-OH retinal, which has a significantly higher solubility in aqueous medium. We have then correlated these parameters with the rates of pigment regeneration and sensitivity recovery that are observed when bleached intact salamander rod photoreceptors are treated with physiological solutions containing these retinoids. We report the following results: (a) 11-cis 4-OH retinal is more soluble in aqueous buffer than 11-cis-retinal. (b) Both 11-cis-retinal and 11-cis 4-OH retinal have extremely high partition coefficients in photoreceptor membranes, though the partition coefficient of 11-cis-retinal is roughly 50-fold greater than that of 11-cis 4-OH retinal. (c) Intact bleached isolated rods treated with solutions containing equimolar amounts of 11-cis-retinal or 11-cis 4-OH retinal form functional visual pigments that promote full recovery of dark current, sensitivity, and response kinetics. However, rods treated with 11-cis 4-OH retinal regenerated on average fivefold faster than rods treated with 11-cis-retinal. (d) Pigment regeneration from recombinant and wild-type opsin in solution is slower when treated with 11-cis 4-OH retinal than with 11-cis-retinal. Based on these observations, we propose a model in which aqueous solubility of cis-retinoids within the photoreceptor cytosol can place a limit on the rate of visual pigment regeneration in vertebrate photoreceptors. We conclude that the cytosolic gap between the plasma membrane and the disk membranes presents a bottleneck for retinoid flux that results in slowed pigment regeneration and dark adaptation in rod photoreceptors.

Cyclic AMP as a Regulator of the Phototransduction Cascade

Until recently, cAMP has been believed to play an important role in the organization of circadian rhythms in the vertebrate eye but not to be directly involved in controlling the phototransduction cascade in photoreceptors. However, given that cAMP levels in photoreceptor cells vary significantly during the day and that cAMP metabolism in photoreceptor cells may itself be light-dependent, it is logical to suggest that cAMP-dependent protein phosphorylation may be a mechanism for tuning phototransduction processes in accordance with ongoing illumination. The current review addresses contemporary data on the structure of the circadian pacemaker in the retina, the involvement of intraphotoreceptor cAMP in its organization, and the known intracellular targets on which cAMP has or may have regulatory influences. Our recent data indicate that changes in cAMP levels have regulatory influences on the photoreceptor cascade. This action may significantly widen the range of adaptation of photoreceptors to illumination conditions, increasing its sensitivity during the dark part of the day and decreasing its sensitivity in bright light.

Adaptive potentiation in rod photoreceptors after light exposure.

Photoreceptors adapt to changes in illumination by altering transduction kinetics and sensitivity, thereby extending their working range. We describe a previously unknown form of rod photoreceptor adaptation in wild-type (WT) mice that manifests as a potentiation of the light response after periods of conditioning light exposure. We characterize the stimulus conditions that evoke this graded hypersensitivity and examine the molecular mechanisms of adaptation underlying the phenomenon. After exposure to periods of saturating illumination, rods show a 10-35% increase in circulating dark current, an adaptive potentiation (AP) to light exposure. This potentiation grows as exposure to light is extended up to 3 min and decreases with longer exposures. Cells return to their initial dark-adapted sensitivity with a time constant of recovery of ∼7 s. Halving the extracellular Mg concentration prolongs the adaptation, increasing the time constant of recovery to 13.3 s, but does not affect the magnitude of potentiation. In rods lacking guanylate cyclase activating proteins 1 and 2 (GCAP(-/-)), AP is more than doubled compared with WT rods, and halving the extracellular Mg concentration does not affect the recovery time constant. Rods from a mouse expressing cyclic nucleotide-gated channels incapable of binding calmodulin also showed a marked increase in the amplitude of AP. Application of an insulin-like growth factor-1 receptor (IGF-1R) kinase inhibitor (Tyrphostin AG1024) blocked AP, whereas application of an insulin receptor kinase inhibitor (HNMPA(AM)3) failed to do so. A broad-acting tyrosine phosphatase inhibitor (orthovanadate) also blocked AP. Our findings identify a unique form of adaptation in photoreceptors, so that they show transient hypersensitivity to light, and are consistent with a model in which light history, acting via the IGF-1R, can increase the sensitivity of rod photoreceptors, whereas the photocurrent overshoot is regulated by Ca-calmodulin and Ca(2+)/Mg(2+)-sensitive GCAPs.

Dynamical adaptation in photoreceptors.

Adaptation is at the heart of sensation and nowhere is it more salient than in early visual processing. Light adaptation in photoreceptors is doubly dynamical: it depends upon the temporal structure of the input and it affects the temporal structure of the response. We introduce a non-linear dynamical adaptation model of photoreceptors. It is simple enough that it can be solved exactly and simulated with ease; analytical and numerical approaches combined provide both intuition on the behavior of dynamical adaptation and quantitative results to be compared with data. Yet the model is rich enough to capture intricate phenomenology. First, we show that it reproduces the known phenomenology of light response and short-term adaptation. Second, we present new recordings and demonstrate that the model reproduces cone response with great precision. Third, we derive a number of predictions on the response of photoreceptors to sophisticated stimuli such as periodic inputs, various forms of flickering inputs, and natural inputs. In particular, we demonstrate that photoreceptors undergo rapid adaptation of response gain and time scale, over ∼ 300 ms—i. e., over the time scale of the response itself—and we confirm this prediction with data. For natural inputs, this fast adaptation can modulate the response gain more than tenfold and is hence physiologically relevant.

The biological significance of color constancy: An agent-based model with bees foraging from flowers under varied illumination

The perceived color of an object depends on its spectral reflectance and the spectral composition of the illuminant. Thus when the illumination changes, the light reflected from the object also varies. This would result in a different color sensation if no color constancy mechanism is put in place-that is, the ability to form consistent representation of colors across various illuminants and background scenes. We explore the quantitative benefits of various color constancy algorithms in an agent-based model of foraging bees, where agents select flower color based on reward. Each simulation is based on 100 "meadows" with five randomly selected flower species with empirically determined spectral reflectance properties, and each flower species is associated with realistic distributions of nectar rewards. Simulated foraging bees memorize the colors of flowers that they have experienced as most rewarding, and their task is to discriminate against other flower colors with lower rewards, even in the face of changing illumination conditions. We compared the performance of von Kries, White Patch, and Gray World constancy models with (hypothetical) bees with perfect color constancy, and color-blind bees. A bee equipped with trichromatic color vision but no color constancy performed only ∼20% better than a color-blind bee (relative to a maximum improvement at 100% for perfect color constancy), whereas the most powerful recovery of reflectance in the face of changing illumination was generated by a combination of von Kries photoreceptor adaptation and a White Patch calibration (∼30% improvement relative to a bee without color constancy). However, none of the tested algorithms generated perfect color constancy.

We now know what fly photoreceptors compute

It has been known for some time that photoreceptors transmit more information when driven by stimuli which have 'naturalistic' statistical properties and that processing of naturalistic visual stimuli involves nonlinear transformations of the input signals. Until now it was not clear which statistical features of the stimuli the neurons are selectively 'tuned' to respond to. Another major difficulty was to elucidate the computational mechanisms which explain differences in coding naturalistic and Gaussian stimuli. Here we used a functional model of Drosophila photoreceptor to fully characterize their underlying computational capabilities. The model was derived based on photoreceptor responses measured in vivo using naturalistic input stimuli, which the system experiences in its natural environment. In order to characterize the nonlinear transformations performed by photoreceptors we analytically computed the higher-order or generalized frequency response functions (GFRFs) of the identified nonlinear photoreceptor model. Using this approach, we demonstrate, for the first time that the observed increase in power of photoreceptor response, and shift towards higher frequencies as the mean light intensity increases, is the result of changes in the operating point of the photoreceptor, which produces a change in the shape of the magnitude of the frequency response functions. This suggests that the photoreceptor adaptation mechanisms are not tuned to fully compensate for the drop in intensity in order to achieve, in an efficient way - by exploiting the photoreceptor nonlinearity - a change in the shape of the magnitude transfer functions, which are optimal for the given mean intensity level. Furthermore, we examined the significance of both local and non-local high-order phase correlations for fly vision. We simulated the photoreceptor model using synthetic stimuli sequences incorporating local phase correlations (edges) and non-local phase correlations (quadratic phase coupling) superimposed with Gaussian white noise. By decomposing voltage output of photoreceptor somata into linear second- and higher-order responses, we explain the nonlinear mechanisms responsible for coding the local and non-local higher-order statistical features in the stimuli as well as improving their signal-to-noise ratio. To validate the results, we carried out electrophysiological experiments using a specially designed stimuli sequence, which allows extracting the nonlinear component of the photoreceptor response directly from data, without a model.

Common dynamical features of sensory adaptation in photoreceptors and olfactory sensory neurons

Sensory systems adapt, i.e., they adjust their sensitivity to external stimuli according to the ambient level. In this paper we show that single cell electrophysiological responses of vertebrate olfactory receptors and of photoreceptors to different input protocols exhibit several common features related to adaptation, and that these features can be used to investigate the dynamical structure of the feedback regulation responsible for the adaptation. In particular, we point out that two different forms of adaptation can be observed, in response to steps and to pairs of pulses. These two forms of adaptation appear to be in a dynamical trade-off: the more adaptation to a step is close to perfect, the slower is the recovery in adaptation to pulse pairs and viceversa. Neither of the two forms is explained by the dynamical models currently used to describe adaptation, such as the integral feedback model.

Transcriptional analysis of rat photoreceptor cells reveals daily regulation of genes important for visual signaling and light damage susceptibility

Photoreceptor cells face the challenge of adjusting their function and, possibly, their susceptibility to light damage to the marked daily changes in ambient light intensity. To achieve a better understanding of photoreceptor adaptation at the transcriptional level, this study aimed to identify genes which are under daily regulation in photoreceptor cells using microarray analysis and quantitative PCR. Included in the gene set obtained were a number of genes which up until now have not been shown to be expressed in photoreceptor cells, such as Atf3 (activating transcription factor 3) and Pde8a (phosphodiesterase 8A), and others with a known impact on phototransduction and/or photoreceptor survival, such as Grk1 (G protein-coupled receptor kinase 1) and Pgc-1α (peroxisome proliferator-activated receptor γ, coactivator 1alpha). According to their daily dynamics, the genes identified could be clustered in two groups: those with peak expression during the second part of the day which are uniformly promoted to cycle by light/dark transitions and those with peak expression during the second part of the night which are predominantly driven by a clock. Since Grk1 and Pgc-1α belong in the first group, the present results support a concept in which transcriptional regulation of genes by ambient light contributes to the functional adjustment of photoreceptor cells over the 24-h period.

Real-Time Modulation of Zebrafish Cone Phototransduction by Whole-Cell Delivery of zGCAP3 and of its Monoclonal Antibody

Regulation of excitation and adaptation in photoreceptors of the vertebrate retina strongly depends on the cytoplasmic Ca2+ concentration and its interplay with Ca2+ sensor proteins like recoverin, calmodulin and the activating proteins (GCAPs) of guanylate cyclase (GC) (Scholten and Koch, 2011). Of the four GCAP isoforms exclusively transcribed in cones (zGCAP3, 4, 5 and 7), we investigated the physiological function of zGCAP3 in green-sensitive cones of zebrafish, by recording the effect on the photoresponse waveform by cytosol injection of exogenous zGCAP3 (to simulate “real time” protein over-expression), and its monoclonal antibody (to simulate protein knock-down). To identify a suitable antibody we screened several hybridoma fluids with respect to specificity and affinity towards zGCAP3, using immunoblotting and surface plasmon resonance (SPR) spectroscopy. The global fitting of an overlay of SPR sensorgrams obtained with increasing antibody concentrations gave a Ca2+-independent KD of 12 nM for the interaction of zGCAP3 with the antibody. Exogenous proteins were incorporated with a precise timing in the zebrafish cone cytosol by an internal perfusion system coupled to a pressure-polished patch pipette (Benedusi et al. 2011). Typical whole-cell recordings lasting even more than 20 min did not show any significant change in light sensitivity, dark current amplitude, response kinetics and light adaptation, proving also that the enzymatic cascade was not perturbed by the recording protocol. Injection of anti-zGCAP3 caused the complete shutdown of the dark current, indicating that zGCAP3 plays a major role in regulating GC. Injection of purified zGCAP3 did not alter the photoresponse, indicating that the target GC was already saturated with endogenous zGCAP3.Benedusi M, Aquila M, Milani A and Rispoli G (2011). Eur Biophys J 40: 1215-23.Scholten A, Koch KW. (2011). PLoS One 6(8):e23117.

Opsin1-2, Gqα and arrestin levels at Limulus rhabdoms are controlled by diurnal light and a circadian clock

Dark and light adaptation in photoreceptors involve multiple processes including those that change protein concentrations at photosensitive membranes. Light- and dark-adaptive changes in protein levels at rhabdoms have been described in detail in white-eyed Drosophila maintained under artificial light. Here we tested whether protein levels at rhabdoms change significantly in the highly pigmented lateral eyes of wild-caught Limulus polyphemus maintained in natural diurnal illumination and whether these changes are under circadian control. We found that rhabdomeral levels of opsins (Ops1-2), the G protein activated by rhodopsin (G(q)α) and arrestin change significantly from day to night and that nighttime levels of each protein at rhabdoms are significantly influenced by signals from the animal's central circadian clock. Clock input at night increases Ops1-2 and G(q)α and decreases arrestin levels at rhabdoms. Clock input is also required for a rapid decrease in rhabdomeral Ops1-2 beginning at sunrise. We found further that dark adaptation during the day and the night are not equivalent. During daytime dark adaptation, when clock input is silent, the increase of Ops1-2 at rhabdoms is small and G(q)α levels do not increase. However, increases in Ops1-2 and G(q)α at rhabdoms are enhanced during daytime dark adaptation by treatments that elevate cAMP in photoreceptors, suggesting that the clock influences dark-adaptive increases in Ops1-2 and G(q)α at Limulus rhabdoms by activating cAMP-dependent processes. The circadian regulation of Ops1-2 and G(q)α levels at rhabdoms probably has a dual role: to increase retinal sensitivity at night and to protect photoreceptors from light damage during the day.

Fixational eye movements during viewing of dynamic natural scenes

Even during periods of fixation our eyes undergo small amplitude movements. These movements are thought to be essential to the visual system because neural responses rapidly fade when images are stabilized on the retina. The considerable recent interest in fixational eye movements (FEMs) has thus far concentrated on idealized experimental conditions with artificial stimuli and restrained head movements, which are not necessarily a suitable model for natural vision. Natural dynamic stimuli, such as movies, offer the potential to move beyond restrictive experimental settings to probe the visual system with greater ecological validity. Here, we study FEMs recorded in humans during the unconstrained viewing of a dynamic and realistic visual environment, revealing that drift trajectories exhibit the properties of a random walk with memory. Drifts are correlated at short time scales such that the gaze position diverges from the initial fixation more quickly than would be expected for an uncorrelated random walk. We propose a simple model based on the premise that the eye tends to avoid retracing its recent steps to prevent photoreceptor adaptation. The model reproduces key features of the observed dynamics and enables estimation of parameters from data. Our findings show that FEM correlations thought to prevent perceptual fading exist even in highly dynamic real-world conditions.

Regulation of the methylation status of G protein-coupled receptor kinase 1 (rhodopsin kinase)

Rhodopsin kinase (GRK1) is a member of G protein-coupled receptor kinase family and a key enzyme in the quenching of photolysed rhodopsin activity and desensitisation of the rod photoreceptor neurons. Like some other rod proteins involved in phototransduction, GRK1 is posttranslationally modified at the C terminus by isoprenylation (farnesylation), endoproteolysis and α-carboxymethylation. In this study, we examined the potential mechanisms of regulation of GRK1 methylation status, which have remained unexplored so far. We found that considerable fraction of GRK1 is endogenously methylated. In isolated rod outer segments, its methylation is inhibited and demethylation stimulated by low-affinity nucleotide binding. This effect is not specific for ATP and was observed in the presence of a non-hydrolysable ATP analogue AMP-PNP, GTP and other nucleotides, and thus may involve a site distinct from the active site of the kinase. GRK1 demethylation is inhibited in the presence of Ca2+ by recoverin. This inhibition requires recoverin myristoylation and the presence of the membranes, and may be due to changes in GRK1 availability for processing enzymes upon its redistribution to the membranes induced by recoverin/Ca2+. We hypothesise that increased GRK1 methylation in dark-adapted rods due to elevated cytoplasmic Ca2+ levels would further increase its association with the membranes and recoverin, providing a positive feedback to efficiently suppress spurious phosphorylation of non-activated rhodopsin molecules and thus maximise senstivity of the photoreceptor. This study provides the first evidence for dynamic regulation of GRK1 α-carboxymethylation, which might play a role in the regulation of light sensitivity and adaptation in the rod photoreceptors.

Low aqueous solubility of 11-cis-retinal limits the rate of pigment formation and dark adaptation in salamander rods

We report experiments designed to test the hypothesis that the aqueous solubility of 11-cis-retinoids plays a significant role in the rate of visual pigment regeneration. Therefore, we have compared the aqueous solubility and the partition coefficients in photoreceptor membranes of native 11-cis-retinal and an analogue retinoid, 11-cis 4-OH retinal, which has a significantly higher solubility in aqueous medium. We have then correlated these parameters with the rates of pigment regeneration and sensitivity recovery that are observed when bleached intact salamander rod photoreceptors are treated with physiological solutions containing these retinoids. We report the following results: (a) 11-cis 4-OH retinal is more soluble in aqueous buffer than 11-cis-retinal. (b) Both 11-cis-retinal and 11-cis 4-OH retinal have extremely high partition coefficients in photoreceptor membranes, though the partition coefficient of 11-cis-retinal is roughly 50-fold greater than that of 11-cis 4-OH retinal. (c) Intact bleached isolated rods treated with solutions containing equimolar amounts of 11-cis-retinal or 11-cis 4-OH retinal form functional visual pigments that promote full recovery of dark current, sensitivity, and response kinetics. However, rods treated with 11-cis 4-OH retinal regenerated on average fivefold faster than rods treated with 11-cis-retinal. (d) Pigment regeneration from recombinant and wild-type opsin in solution is slower when treated with 11-cis 4-OH retinal than with 11-cis-retinal. Based on these observations, we propose a model in which aqueous solubility of cis-retinoids within the photoreceptor cytosol can place a limit on the rate of visual pigment regeneration in vertebrate photoreceptors. We conclude that the cytosolic gap between the plasma membrane and the disk membranes presents a bottleneck for retinoid flux that results in slowed pigment regeneration and dark adaptation in rod photoreceptors.

A tale of two kinases in rods and cones.

Members of the G protein-coupled receptor kinase family play essential roles in signal turnoff for the majority of G protein-coupled receptors. GRK1, first identified almost 40 years ago, and GRK7, the most recently identified member of the GRK family, are retina-specific GRKs involved in the recovery and adaptation of rod and cone photoreceptors in the vertebrate retina. This report reviews the expression patterns of these two kinases, as well as the effect of their interaction with their substrates and binding partners. The phosphorylation of GRK1 and GRK7 by cAMP-dependent protein kinase (PKA) is also discussed.