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To evaluate how terrestrially descended, marine-living tetrapods have adapted their vision for life in the ocean environment, the rod and cone visual pigments of diving turtles, birds, and mammals were examined. Genetics was used primarily. When possible, in situ electroretinography (ERG) was also used.Of the three visual pigments possessed by most mammals, cetacean rod and middle/long-wavelength sensitive (M/L) cone visual pigments had previously been shown to be shifted towards the wavelengths (λ) of light that predominant in marine habits, λ~475 nm. The genetic sequences of the short-wavelength sensitive (S) cones of numerous cetaceans were examined from nuclear DNA. The distribution of mis­-sense mutations found in their S cone opsin genes indicates that all members ofthe cetacean order lack S cones. Genetic evaluation of the retinal mRNA of seven pinniped species revealed that these mammals also lack S cones. The convergent loss of S cones in pinnipeds and cetaceans suggests that this loss may be adaptive for vision in the marine environment. Rod and M/L cone pigments of pinnipeds were also examined. In contrast to the cetaceans, one pinniped, the deep-diving northern elephant seal was found to possess a short-wavelength-shifted visual pigment, its rod pigment. The rod and M/L cone visual pigments of the other pinnipeds were similar to those of terrestrial carnivores. An ERG investigation of three pinnipeds including the elephant seal supported the genetic results.Finally, the rod visual pigments of five sea turtle and three penguin species were examined with genetics. None was found to be markedly marine-adapted. Additional examination of cone sensitivity in sea turtles with ERG indicated limited departure from the terrestrial condition. Clearly, the cetaceans are the most marine adapted ofthe groups examined. The pinnipeds and sea turtles showed limited adaptation, and the penguins were not apparently different from terrestrial birds. As the cetaceans are the only completely aquatic lineage among these groups, it seems that the terrestrial life-stage may still be of selective significance to some or all of the other groups. Particularly in the case of the sea turtles and penguins, which are highly photopic by ancestry, phylogenetic inertia may also limit the plasticity of the visual systems in adapting for vision in the marine environment.XIV

The spectral mechanisms of the ferret (Mustela putorious furo) were studied with electroretinogram (ERG) flicker photometry. Variations in adaptation state and flicker rate were used to define corneally based spectral sensitivities for the three classes of receptor present in the retina of this mustelid-rods (lambda(max) = 505 nm), S cones (430 nm), and L cones (558 nm). The retinal distributions of the two classes of cone were determined using opsin antibody labeling. Ferret retinas contain a total of about 1.3 million cones with L cones outnumbering S cones in a ratio of approximately 14:1. ERGS were also recorded using 18.75-Hz flickering stimuli that were designed to isolate signals from individual cone classes. The contrast/response functions for signals originating from both S and L cones were linear over low-to-moderate levels of contrast, but with greatly different slopes for the two cone types. The L:S contrast gain ratio derived from a comparison of these slopes, as well as inferences drawn from another experiment in which responses to various combinations of L- and S-cone activation were analyzed, suggest that contributions of these two cone types to the flicker ERG have a relative weighting of about 4:1 to 5:1 (L/S).

Abstract Background Morphological divergences of snake retinal structure point to complex evolutionary processes and adaptations. The Colubridae family has a remarkable variety of retinal structure that can range from all-cone and all-rod to duplex (cone/rod) retinas. To explore whether nocturnal versus diurnal activity is responsible for constraints on molecular evolution and plays a role in visual opsin spectral tuning of colubrids, we carried out molecular evolution analyses of the visual opsin genes LWS, RH1, and SWS1 from 17 species and performed morphological analyses. Results Phylogenetic reconstructions of the RH1 and LWS recovered major clades characterized by primarily diurnal or primarily nocturnal activity patterns, in contrast with the topology for SWS1, which is very similar to the species tree. We found stronger signals of purifying selection along diurnal and nocturnal lineages for RH1 and SWS1, respectively. A blue-shift of the RH1 spectral peak is associated with diurnal habits. Spectral tuning of cone opsins did not differ among diurnal and nocturnal species. Retinas of nocturnal colubrids had many rows of photoreceptor nuclei, with large numbers of rods, labeled by wheat germ agglutinin (WGA), and two types of cones: large cones sensitive to long/medium wavelengths (L/M) and small cones sensitive to ultra-violet/violet wavelengths (UV/VS). In contrast, retinas of diurnal species had only one row of photoreceptor nuclei, with four types of cones: large and double L/M cones, small UV/VS cones, and a second group of small cones, labeled by WGA. Conclusions For LWS gene, selection tests did not confirm different constraints related to activity pattern. For SWS1, stronger purifying selection in nocturnal lineages indicates divergent evolutionary pressures related to the activity pattern, and the importance of the short wavelength sensitivity at low light condition. Activity pattern has a clear influence on the signatures of selection and spectral tuning of RH1, with stronger purifying selection in diurnal lineages, which indicates selective pressure to preserve rhodopsin structure and function in pure-cone retinas. We suggest that the presence of four cone types in primarily diurnal colubrids might be related to the gain of color discrimination capacity.

Retinas of the river lamprey Lampetra fluviatilis were studied by microspectrophotometry, electroretinography and single-photoreceptor electrophysiology to reconcile the apparently contradictory conclusions on the nature of lamprey photoreceptor cells drawn in the early work by Govardovskii and Lychakov (J Comp Physiology A 154:279–286, 1984) and in recent studies. In agreement with recent works, we confirmed former identification of short photoreceptors as rods and of long photoreceptors as cones. In line with the results of 1984, we show that within a certain range of light intensities the lamprey retina exhibits "color discrimination". We found that the overlap of working intensity ranges of rods and cones is not a unique feature of lamprey short receptors, and suggest that rod-cone (possibly color) vision may be common among vertebrates. We show that the decay of meta-intermediates in lamprey cones occurs almost 100 times faster than in typical rod metarhodopsins. Rate of decay of metarhodopsins of lamprey rods take an intermediate position between typical rods and cones. This makes lamprey rhodopsin similar to transmuted cone visual pigment in "rods" of nocturnal geckos. We argue that defining various types of photoreceptors as simply "rods" and "cones" may be functionally correct, but neglects their genetic, biochemical and morphological features and evolutionary history. [ABSTRACT FROM AUTHOR]

Pluripotent stem cells (PSCs) are a potential replacement tissue source for degenerative diseases. Age-related macular degeneration (AMD) is a blinding disease triggered by degeneration of the retinal pigment epithelium (RPE), a monolayer tissue that functionally supports retinal photoreceptors. Recently published clinical and preclinical studies have tested PSC-derived RPE as a potential treatment for AMD. Multiple approaches have been used to manufacture RPE cells, to validate them functionally, to confirm their safety profile, and to deliver them to patients either as suspension or as a monolayer patch. Since most of these studies are at an early regulatory approval stage, the primary outcome has been to determine the safety of RPE transplants in patients. However, preliminary signs of efficacy were observed in a few patients. Here, we review the current progress in the PSC-derived RPE transplantation field and provide a comparative assessment of various approaches under development as potential therapeutics for AMD. [ABSTRACT FROM AUTHOR]

Photoisomerization of the 11-cis-retinal chromophore of rod and cone visual pigments to an all-trans-configuration is the initiating event for vision in vertebrates. The regeneration of 11-cis-retinal, necessary for sustained visual function, is an endergonic process normally conducted by specialized enzyme systems. However, 11-cis-retinal also can be formed through reverse photoisomerization from all-trans-retinal. A nonvisual opsin known as retinal pigment epithelium (RPE)-retinal G-protein-coupled receptor (RGR) was previously shown to mediate visual chromophore regeneration in photic conditions, but conflicting results have cast doubt on its role as a photoisomerase. Here, we describe high-level production of 11-cis-retinal from RPE membranes stimulated by illumination at a narrow band of wavelengths. This activity was associated with RGR and enhanced by cellular retinaldehyde-binding protein (CRALBP), which binds the 11-cis-retinal produced byRGRand prevents its re-isomerization to all-trans-retinal. The activity was recapitulated with cells heterologously expressing RGR and with purified recombinant RGR. Using an RGR variant, K255A, we confirmed that a Schiff base linkage at Lys-255 is critical for substrate binding and isomerization. Single-cell RNA-Seq analysis of the retina and RPE tissue confirmed that RGR is expressed in human and bovine RPE and Müller glia, whereas mouse RGR is expressed in RPE but not in Müller glia. These results provide key insights into the mechanisms of physiological retinoid photoisomerization and suggest a novel mechanism by which RGR, in concert with CRALBP, regenerates the visual chromophore in the RPE under sustained light conditions. [ABSTRACT FROM AUTHOR]

Macular pigment (MP) confers potent antioxidant and anti-inflammatory effects at the macula, and may therefore protect retinal tissue from the oxidative stress and inflammation associated with ocular disease and ageing. There is a body of evidence implicating oxidative damage and inflammation as underlying pathological processes in diabetic retinopathy. MP has therefore become a focus of research in diabetes, with recent evidence suggesting that individuals with diabetes, particularly type 2 diabetes, have lower MP relative to healthy controls. The present review explores the currently available evidence to illuminate the metabolic perturbations that may possibly be involved in MP's depletion. Metabolic co-morbidities commonly associated with type 2 diabetes, such as overweight/obesity, dyslipidaemia, hyperglycaemia and insulin resistance, may have related and independent relationships with MP. Increased adiposity and dyslipidaemia may adversely affect MP by compromising the availability, transport and assimilation of these dietary carotenoids in the retina. Furthermore, carotenoid intake may be compromised by the dietary deficiencies characteristic of type 2 diabetes, thereby further compromising redox homeostasis. Candidate causal mechanisms to explain the lower MP levels reported in diabetes include increased oxidative stress, inflammation, hyperglycaemia, insulin resistance, overweight/obesity and dyslipidaemia; factors that may negatively affect redox status, and the availability, transport and stabilisation of carotenoids in the retina. Further study in diabetic populations is warranted to fully elucidate these relationships. [ABSTRACT FROM AUTHOR]

The discovery of melanopsin as a third type of retinal photoreceptor, contributing to both perceptual vision and reflex light responses, represents a new opportunity to optimise the design of artificial light sources for practical applications and to generate experimental stimuli. In the case of emissive displays, multiprimary designs incorporating a cyan primary could be used to allow melanopic radiance to be controlled independent of colour and luminance. Here we explore the performance a five-primary (violet, cyan, green, yellow, red) display device and find an anomaly in colour appearance when the cyan primary is employed. The anomaly took the form of a reddish/pinkish tinge in the central visual field, consistent with descriptions of Maxwell's spot. This effect was apparent in some full colour images and in uniform discs over a range of chromaticities. Its appearance in coloured discs correlated with differences in calculated colour coordinate between central and peripheral vision. A simulation indicated that inclusion of any primary with predominant output in the 470-500 nm range has the potential to produce such a discrepancy in central vs peripheral appearance. Applying an additional constraint in colour processing to reproduce naturally occurring differences in central vs peripheral colour coordinate eliminated appearance of the spot and produced acceptable colour images. [ABSTRACT FROM AUTHOR]

Owls constitute a diverse group of raptors, active at different times of the day with distinct light conditions that might be associated with multiple visual adaptations. We investigated whether shifts in the spectral sensitivity of the L cone visual pigment, as inferred by analysis of gene structure, could be one such adaptive mechanism. Using Sanger sequencing approach, we characterized the long wavelength-sensitive (LWS) opsin gene expressed in the retina of five owl species, specifically chosen to represent distinct patterns of activity. Nocturnality was epitomized by the American barn owl (Tyto furcata), the striped owl (Asio clamator), and the tropical screech owl (Megascops choliba); diurnality, by the ferruginous pygmy owl (Glaucudium brasilianum); and cathemerality, by the burrowing owl (Athene cunicularia). We also analyzed the presence of the L cone in the retinas of four species of owl (T. furcata, A. cunicularia, G. brasilianum and M. choliba) using immnunohistochemistry. Five critical sites for the spectral tuning of the LWS opsin (164, 181, 261, 269, and 292) were analyzed and compared to the sequence of other birds. The sequence of A. cunicularia showed a substitution on residue 269, with the presence of an alanine instead threonine, which generates an estimated maximum absorption (λmax) around 537 nm. No other variation was found in the spectral tuning sites of the LWS opsin, among the other species, and the λmax was estimated at around 555 nm. The presence of L cones in the retinas of the four species of owls was revealed using immunohistochemistry and we observed a reduced number of L cones in T. furcata compared to A. cunicularia, G. brasilianum and M. choliba. [ABSTRACT FROM AUTHOR]

Background: It has been shown that rod-mediated dark adaptation is significantly delayed in ageing, a change which is exacerbated in age-related macular degeneration (AMD). Levels of lutein and zeaxanthin, the two main constituents of macular pigment have been found in rod outer segments, indicating that the macular pigment may have an influence on rod-mediated dark adaptation. The aim of this study was to determine if rod-mediated dark adaptation is associated with central macular pigment levels in individuals with intermediate stage AMD.Methods: A cross-sectional observational study included individuals with acuity better than 6/15 Snellen and intermediate stage AMD based on graded fundus photographs using an internationally accepted grading scale. Rod-mediated dark adaptation was assessed at five degrees eccentricity in the superior retina (inferior visual field) using the rod intercept time measure from the MacuLogix AdaptDx. Macular pigment optical density was measured at 0.5 degrees eccentricity using a heterochromatic flicker photometry-based method.Results: Twenty-seven individuals (mean age 76.7 years) with intermediate stage AMD and 23 age-matched normal controls (mean age 74.0 years) were recruited. Rod-mediated dark adaptation was significantly delayed in intermediate stage AMD compared with healthy controls (32.9 minutes versus 10.7 minutes, p < 0.01). There was no statistically significant correlation between the rod intercept time and the level of macular pigment in those with intermediate AMD (r = -0.04, p = 0.85).Conclusion: The results did not support the hypothesis that higher macular pigment is associated with improved rod-mediated performance or that higher levels of macular pigment protect rod-mediated function in intermediate AMD. [ABSTRACT FROM AUTHOR]

The white noise electroretinogram (wnERG) provides a measure of the impulse response function under conditions of retinal equilibrium; it is yet to be determined how the electrical response generated by melanopsin ganglion cell photoreception is expressed in the impulse response. To this end, we recorded the human wnERG to continuous temporal white noise (TWN) stimuli that were melanopsin-directed (rod and cone silent) or cone-directed (rod and melanopsin silent). The impulse response of the electroretinogram was derived by cross-correlating the TWN stimulus with the wnERG response. We observed that the LMS-cone directed wnERG contained the expected N1 wave (24.1 ± 2.4 ms; mean ± SEM) and P1 wave (49.7 ± 1.8 ms). Melanopsin-directed stimuli produced a unique wnERG with a slower negative deflection (Nm) at 62.9 ± 3.3 ms followed by a positive deflection (Pm) at 126.3 ± 5.1 ms. Additional experiments indicated this melanopsin-directed wnERG response was not due to cone intrusion. The Nm and NmPm amplitudes increased with illuminance (32,000-80,000 Td; no rod intrusion) and melanopsin contrast (10-36% Michelson contrast). As there are known pathways connecting melanopsin cells to the outer retina, we then measured the wnERG to combined melanopsin and cone-directed stimuli to quantify melanopsin interactions with cone signalling. With the combined stimuli, the N1P1 amplitudes were suppressed by ~59%, which may be a result of a destructive interference between the positive (P1) and negative (Nm) waves generated by the cone and melanopsin pathways. We conclude that the human wnERG to melanopsin-directed stimuli may reflect the combined response of intra-retinal melanopsin pathways, independent of rod and cone photoreception. [ABSTRACT FROM AUTHOR]

Imaging of rod photoreceptor outer-segment disc membranes by atomic force microscopy and cryo-electron tomography has revealed that the visual pigment rhodopsin, a prototypical class A G protein--coupled receptor (GPCR), can organize as rows of dimers. GPCR dimerization and oligomerization offer possibilities for allosteric regulation of GPCR activity, but the detailed structures and mechanism remain elusive. In this investigation, we made use of the high rhodopsin density in the native disc membranes and of a bifunctional cross-linker that preserves the native rhodopsin arrangement by covalently tethering rhodopsins via Lys residue side chains. We purified cross-linked rhodopsin dimers and reconstituted them into nanodiscs for cryo-EM analysis. We present cryo-EM structures of the cross-linked rhodopsin dimer as well as a rhodopsin dimer reconstituted into nanodiscs from purified monomers. We demonstrate the presence of a preferential 2-fold symmetrical dimerization interface mediated by transmembrane helix 1 and the cytoplasmic helix 8 of rhodopsin. We confirmed this dimer interface by double electron--electron resonance measurements of spin-labeled rhodopsin. We propose that this interface and the arrangement of two protomers is a prerequisite for the formation of the observed rows of dimers. We anticipate that the approach outlined here could be extended to other GPCRs or membrane receptors to better understand specific receptor dimerization mechanisms. [ABSTRACT FROM AUTHOR]

Background. Pueraria lobata is used in traditional Asian medicine to treat cardiovascular diseases, diarrhea, diabetes mellitus, and diabetic complications such as diabetic retinopathy. Oxidative stress in retinal pigment epithelial cells is implicated in the pathogenesis of retinopathy and age-related macular degeneration (AMD). Here, we evaluated whether the P. lobata extract can prevent cell death and decrease membrane permeability in oxidative stress-induced human retinal pigment epithelial cells. Methods. The effects of P. lobata extract on hydrogen peroxide- (H2O2-) induced oxidative stress were investigated using 2′,7′–dichlorofluorescin diacetate, western blotting, and immunohistochemistry in human retinal pigment epithelial cells. The effects of puerarin, daidzein, and daidzin isolated from P. lobata extract were also studied by determining cell death, reactive oxygen species (ROS) generation, and p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) phosphorylation. Results. Our results showed that the P. lobata extract inhibited ROS generation, suppressed the disruption of zonula occludens-1 (ZO-1), and reduced membrane permeability in H2O2-induced human retinal pigment epithelial cells. Additionally, the P. lobata extract prevented the inhibition of p38 MAPK and JNK phosphorylation. Conclusion. Our findings suggest that the P. lobata extract has the potential to prevent AMD development by inhibiting the mechanism underlying oxidative stress-mediated ocular disorders. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction is an important cause of heritable vision loss. Mutations affecting mitochondrial bioenergetics may lead to isolated vision loss or life-threatening systemic disease, depending on a mutation's severity. Primary optic nerve atrophy resulting from death of retinal ganglion cells is the most prominent ocular manifestation of mitochondrial disease. However, dysfunction of other retinal cell types has also been described, sometimes leading to a loss of photoreceptors and retinal pigment epithelium that manifests clinically as pigmentary retinopathy. A popular mouse model of mitochondrial disease that lacks NADH:ubiquinone oxidoreductase subunit S4 (NDUFS4), a subunit of mitochondrial complex I, phenocopies many traits of the human disease Leigh syndrome, including the development of optic atrophy. It has also been reported that ndufs4-/-mice display diminished light responses at the level of photoreceptors or bipolar cells. By conducting electroretinography (ERG) recordings in live ndufs4-/- mice, we now demonstrate that this defect occurs at the level of retinal photoreceptors. We found that this deficit does not arise from retinal developmental anomalies, photoreceptor degeneration, or impaired regeneration of visual pigment. Strikingly, the impairment of ndufs4-/- photoreceptor function was not observed in ex vivo ERG recordings from isolated retinas, indicating that photoreceptors with complex I deficiency are intrinsically capable of normal signaling. The difference in electrophysiological phenotypes in vivo and ex vivo suggests that the energy deprivation associated with severe mitochondrial impairment in the outer retina renders ndufs4-/- photoreceptors unable to maintain the homeostatic conditions required to operate at their normal capacity. [ABSTRACT FROM AUTHOR]

Purpose. To identify and correlate age-related changes in outer retinal layers' thickness and choroidal thickness (CT) in the normal eyes using spectral-domain optical coherence tomography (SD-OCT) and to investigate factors affecting these changes. Study Design. Observational cross-sectional study. Subjects and Methods. We studied 125 healthy Egyptians between 20 and 79 years old. Patients were divided into 3 groups: group 1 (20–40 years), group 2 (40–60 years), and group 3 (>60 years). All patients had full ophthalmic examination. SD-OCT was done to measure the 9 ETDRS macular grid sectors of retinal pigment epithelium and photoreceptor outer segment (RPE-OS), outer nuclear layer and photoreceptor inner segment (ONL-IS), and choroidal thickness (CT) (by enhanced depth imaging). Results. RPE-OS was significantly thinner in group 3 than in the other 2 groups (central: P<0.001). Moreover, the 3 groups were significantly different from each other regarding the CT (central: P<0.001); significant thinning was noticed in the choroid with age. The 3 groups did not show significant difference concerning the ONL-IS thickness. RPE-OS and CT showed statistically significant negative correlation with age (central RPE-OS: r = −0 C.345, P<0.001, and central CT: r = −0.725, P<0.001) while ONL-IS showed statistically nonsignificant correlation with age (central ONL-IS: r = −0.08, P=0.376). Multiple regression analysis revealed that the most important determinant of central 1 mm RPE-OS thickness in this study was age (β = −0.087, P=0.010) rather than choroidal thinning (β = 0.001, P=0.879). Conclusion. RPE-OS layer thickness shows significant thinning with increasing age, and with decrease in CT, however, age is the most determinant factor of this thinning. [ABSTRACT FROM AUTHOR]

Functional variation in rhodopsin, the dim-light-specialized visual pigment, frequently occurs in species inhabiting light-limited environments. Variation in visual function can arise through two processes: relaxation of selection or adaptive evolution improving photon detection in a given environment. Here, we investigate the molecular evolution of rhodopsin in Gymnotiformes, an order of mostly nocturnal South American fishes that evolved sophisticated electrosensory capabilities. Our initial sequencing revealed a mutation associated with visual disease in humans. As these fishes are thought to have poor vision, this would be consistent with a possible sensory trade-off between the visual system and a novel electrosensory system. To investigate this, we surveyed rhodopsin from 147 gymnotiform species, spanning the order, and analysed patterns of molecular evolution. In contrast with our expectation, we detected strong selective constraint in gymnotiform rhodopsin, with rates of non-synonymous to synonymous substitutions lower in gymnotiforms than in other vertebrate lineages. In addition, we found evidence for positive selection on the branch leading to gymnotiforms and on a branch leading to a clade of deep-channel specialized gymnotiform species. We also found evidence that deleterious effects of a human disease-associated substitution are likely to be masked by epistatic substitutions at nearby sites. Our results suggest that rhodopsin remains an important component of the gymnotiform sensory system alongside electrolocation, and that photosensitivity of rhodopsin is well adapted for vision in dim-light environments. [ABSTRACT FROM AUTHOR]

Colour vision is mediated by the expression of different visual pigments in photoreceptors of the vertebrate retina. Each visual pigment is a complex of a protein (opsin) and a vitamin A chromophore; alterations to either component affects visual pigment absorbance and, potentially, the visual capabilities of an animal. Many species of fish undergo changes in opsin expression during retinal development. In the case of salmonid fishes the single cone photoreceptors undergo a switch in opsin expression from SWS1 (ultraviolet sensitive) to SWS2 (blue‐light sensitive) starting at the yolk‐sac alevin stage, around the time when they first experience light. Whether light may initiate this event or produce a plastic response in the various photoreceptors is unknown. In this study, Chinook salmon Oncorhynchus tshawytscha were exposed to light from the embryonic (5 days prior to hatching) into the yolk sac alevin (25 days post hatching) stage and the spectral phenotype of photoreceptors assessed with respect to that of unexposed controls by in situ hybridization with opsin riboprobes. Light exposure did not change the spectral phenotype of photoreceptors, their overall morphology or spatial arrangement. These results concur with those from a variety of fish species and suggest that plasticity in photoreceptor spectral phenotype via changes in opsin expression may not be a widespread occurrence among teleosts. [ABSTRACT FROM AUTHOR]

The precise control of visual sensitivity to variations in external lighting is critical for optimising human visual function in a changing environment. In photopic illumination, the cone photoreceptors and their post-receptoral pathways have a primary role in regulating these adjustments; it is not fully understood how a small population of melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs) can interact with the three cone photoreceptor classes to modulate human visual function. Here we investigated interactions between these inner and outer retinal photoreceptor classes in participants with trichromatic colour vision under conditions that independently controlled the excitations of ipRGCs, cones and rods in the retina. In the peripheral retina, we show that interaction between melanopsin- and cone-directed signals affect conscious, image-forming vision. The interaction patterns are inconsistent with any potential effects arising from artefacts due to open-field and penumbral-cone contrasts, or rod intrusion. For cone signals mediated via each of the three primary visual pathways, melanopsin activation enhances contrast sensitivity. The contrast response functions indicate this enhancement is a more generalised facilitation effect that onsets at ∼9% melanopsin contrast. The implication for human vision is that the contrast sensitivity of cone-mediated visual processes can be modulated by the level of melanopsin excitation in the stimulus light. [ABSTRACT FROM AUTHOR]

Purpose. No standard therapy for RPE tear, a complication of neovascular age-related macular degeneration, exists even though RPE tears cause severe vision loss, and promotion of cell proliferation and/or migration could be a candidate RPE tear therapy. The aim of this study is to evaluate the effect of Rho-associated coiled-coil containing kinase (ROCK) inhibitor Y27632 on retinal pigment epithelial (RPE) cell motility during wound healing. Methods. Human RPE cells were cultured in media with and without 10 μM Y27632. A luminescent cell viability assay and vinculin immunocytochemistry were used to test the Y27632 effect on RPE cell adhesion. The mean size of vinculin puncta was quantified from immunofluorescence images. RPE cell motility during wound healing was evaluated using time-lapse imaging and measuring cell migration distances and cell coverage rate in wound fields. Results. The number of adhered RPE and mean size of vinculin puncta were, respectively, 20519 cells and 3.65 μm2 under nontreatment and 23569 cells and 0.66 μm2 under Y27632 treatment. Cell migration distance and cell coverage percentage for untreated and Y27632-treated cells were 98.9 and 59.4% and 203.4 and 92.5%, respectively. Conclusions. Inhibition of ROCK signaling by using 10 μM Y27632 promoted RPE cell motility during wound healing by reducing RPE cell adhesion strength. [ABSTRACT FROM AUTHOR]

Purpose. Ocular aging is a natural process of functional decline in vision. When the process reaches a point that compromised vision affects normal daily activity, it manifests as age-related ocular diseases, such as age-related macular degeneration, cataracts, glaucoma, and pseudoexfoliation syndrome. We previously reported that repressed Wnt signaling accelerated the maturation of corneal epithelium during tissue development. Here, we explore the hypothesis that repressed Wnt signaling is associated with accelerated aging in mouse eyes. Methods. Wnt ligand antagonist secreted frizzled-related protein 1 (sFRP1) was expressed in the corneal stroma by a tissue-specific, inducible, bitransgenic system. Tissue structure was analyzed for signs of aging. Signal transduction analysis was performed to determine the cellular response to sFRP1. Results. Mouse eyes with sFRP1 expression showed signs of accelerated aging, resembling those found in pseudoexfoliation (PEX) syndrome, a known age-related disease. Specific findings include granular deposition on the surface of the anterior lens capsule, pigment loss from the anterior surface of the iris, the presence of fibrillary material in the anterior chamber, and changes in cell size (polymegethism) and shape (pleomorphism) of the corneal endothelial cells. In vitro studies demonstrated that sFRP1 did not inhibit Wnt5a function and that cells responded to sFRP1 and Wnt5a in a very similar manner. Conclusion. The expression of sFRP1 accelerates the aging process in mouse eyes and future studies are warranted to elucidate the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Mutations in the RHO gene encoding for the visual pigment protein, rhodopsin, are among the most common cause of autosomal dominant retinitis pigmentosa (ADRP). Previous studies of ADRP mutations in different domains of rhodopsin have indicated that changes that lead to more instability in rhodopsin structure are responsible for more severe disease in patients. Here, we further test this hypothesis by comparing side-by-side and therefore quantitatively two RHO mutations, N15S and P23H, both located in the N-terminal intradiscal domain. The in vitro biochemical properties of these two rhodopsin proteins, expressed in stably transfected tetracycline-inducible HEK293S cells, their UV-visible absorption, their Fourier transform infrared, circular dichroism and Metarhodopsin II fluorescence spectroscopy properties were characterized. As compared to the severely impaired P23H molecular function, N15S is only slightly defective in structure and stability. We propose that the molecular basis for these structural differences lies in the greater distance of the N15 residue as compared to P23 with respect to the predicted rhodopsin folding core. As described previously for WT rhodopsin, addition of the cytoplasmic allosteric modulator chlorin e6 stabilizes especially the P23H protein, suggesting that chlorin e6 may be generally beneficial in the rescue of those ADRP rhodopsin proteins whose stability is affected by amino acid replacement. [ABSTRACT FROM AUTHOR]

There are fundamental differences in the structures of outer segments between rod and cone photoreceptor cells in the vertebrate retina. Visual pigments are the only essential membrane proteins that differ between rod and cone outer segments, making it likely that they contribute to these structural differences. Human rhodopsin is N-glycosylated on Asn² and Asn15, whereas human (h) red and green cone opsins (hOPSR and hOPSG, respectively) are N-glycosylated at Asn34. Here, utilizing a monoclonal antibody (7G8 mAB), we demonstrate that hOPSR and hOPSG from human retina also are O-glycosylated with full occupancy. We determined that 7G8 mAB recognizes the N-terminal sequence 21DSTQSSIF28 of hOPSR and hOPSG from extracts of human retina, but only after their O-glycans have been removed with O-glycosidase treatment, thus revealing this post-translational modification of red and green cone opsins. In addition, we show that hOPSR and hOPSG from human retina are recognized by jacalin, a lectin that binds to O-glycans, preferentially to Gal-GalNAc. Next, we confirmed the presence of O-glycans on OPSR and OPSG from several vertebrate species, including mammals, birds, and amphibians. Finally, the analysis of bovine OPSR by MS identified an O-glycan on Ser22, a residue that is semi-conserved (Ser or Thr) among vertebrate OPSR and OPSG. These results suggest that O-glycosylation is a fundamental feature of red and green cone opsins, which may be relevant to their function or to cone cell development, and that differences in this post-translational modification also could contribute to the different morphologies of rod and cone photoreceptors. [ABSTRACT FROM AUTHOR]

Most diurnal birds have cone-dominated retinae and tetrachromatic colour vision based on ultra-violet/violet-sensitive UV/V cones expressing short wavelength-sensitive opsin 1 (SWS1), S cones expressing short wavelength-sensitive opsin 2 (SWS2), M cones expressing medium wavelength-sensitive opsin (RH2) and L cones expressing long wavelength-sensitive opsin (LWS). Double cones (D) express LWS but do not contribute to colour vision. Each cone is equipped with an oil droplet, transparent in UV/V cones, but pigmented by carotenoids: galloxanthin in S, zeaxanthin in M, astaxanthin in L and a mixture in D cones. Owls (Strigiformes) are crepuscular or nocturnal birds with rod-dominated retinae and optical adaptations for high sensitivity. For eight species, the absence of functional SWS1 opsin has recently been documented, functional RH2 opsin was absent in three of these. Here we confirm the absence of SWS1 transcripts for the Long-eared owl (Asio otus) and demonstrate its absence for the Short-eared owl (Asio flammeus), Tawny owl (Strix aluco) and Boreal owl (Aegolius funereus). All four species had transcripts of RH2, albeit with low expression. All four species express all enzymes needed to produce galloxanthin, but lack CYP2J19 expression required to produce astaxanthin from dietary precursors. We also present ocular media transmittance of the Eurasian eagle owl (Bubo bubo) and Short-eared owl and predict spectral sensitivities of all photoreceptors of the Tawny owl. We conclude that owls, despite lacking UV/V cones, can detect UV light. This increases the sensitivity of their rod vision allowing them, for instance, to see UV-reflecting feathers as brighter signals at night. [ABSTRACT FROM AUTHOR]

Snakes inhabit a great variety of habitats, whose spectral quality of light may vary a lot and influence specific adaptations of their visual system. In this study, we investigated the genetics of the visual opsins and the morphology of retinal photoreceptors, of two nocturnal snakes from the Viperidae family, Bothrops jararaca and Crotalus durissus terrificus, which inhabit preferentially the Atlantic Rain Forest and the Brazilian Savannah, respectively. Total RNA was extracted from homogenized retinas and converted to cDNA. The opsin genes expressed in snake retinas, LWS, RH1, and SWS1, were amplified by polymerase chain reactions (PCRs) and sequenced. The absorption peak (λmax) of the opsins were estimated based on amino acids located at specific spectral tuning sites. Photoreceptor cell populations were analyzed using immunohistochemistry with anti-opsin antibodies. Results showed the same morphological cell populations and same opsins absorption peaks, in both viperid species: double and single cones with LWS photopigment and λmax at ∼555 nm; single cones with SWS1 photopigment and λmax at ∼360 nm; and rods with the rhodopsin RH1 photopigment and λmax at ∼500 nm. The results indicate adaptations to nocturnal habit in both species despite the differences in habitat, and the possibility of a dichromatic color vision at photopic conditions. [ABSTRACT FROM AUTHOR]

Retinal and cortical signals initiated by a single cone type can be recorded using the spectral compensation (or silent substitution) paradigm. Moreover, responses to instantaneous excitation increments combined with gradual excitation decreases are dominated by the response to the excitation increment. Similarly, the response to a sudden excitation decrement dominates the overall response when combined with a gradual excitation increase. Here ERGs and VEPs were recorded from 34 volunteers [25.9 ± 10.4 years old (mean ± 1 SD); 25 males, 9 females] to sawtooth flicker (4 Hz) stimuli that elicited L- or M-cone responses using triple silent substitution. The mean luminance (284 cd/m2) and the mean chromaticity (x = 0.5686, y = 0.3716; CIE 1931 color space) remained constant and thus the state of adaptation was the same in all conditions. Color discrimination thresholds along protan, deutan, and tritan axes were obtained from all participants. Dichromatic subjects were genetically characterized by molecular analysis of their opsin genes. ERG responses to L-cone stimuli were absent in protanopes whereas ERG responses to M-cone stimuli were strongly reduced in deuteranopes. Dichromats showed generally reduced VEP amplitudes. Responses to cone-specific stimuli obtained with standard electrophysiological methods may give the same classification as that obtained with the Cambridge Colour Test and in some cases with the genetic analysis of the L- and M-opsin genes. Therefore, cone-specific ERGs and VEPs may be reliable methods to detect cone dysfunction. The present data confirm and emphasize the potential use of cone-specific stimulation, combined with standard visual electrodiagnostic protocols. [ABSTRACT FROM AUTHOR]

Visual pigments can vary across the retina in many vertebrates, but the behavioural consequences of this retinal heterogeneity are unknown. Guppies (Poecilia reticulata) vary dorsoventrally in visual pigments and forage both on the ground and at the water surface, exposing different retinal regions to two very different visual environments. We tested guppy behaviour towards a moving stimulus presented below or above the guppy. We used 12 different narrow-band wavelength stimuli matching each of the opsin peak sensitivities presented either at the top or the bottom of our experimental apparatus. We analysed behaviours of 50 male and 50 female guppies over 4800 trials where a moving stimulus pattern was presented to each guppy. We found that wavelength, position and speed of the stimuli influenced male and female behaviour and seems to be mediated by the long wavelength sensitive photoreceptors. Males also had stronger behavioural responses than females whereas females performed more foraging-related pecking behaviour. Our results suggest that the spatial requirement of visual tasks and their ecological context are important and appear to be partly correlated with photoreceptor arrangement in the retina. [ABSTRACT FROM AUTHOR]

The variable composition of the chromophore-binding pocket in visual receptors is essential for vision. The visual phototransduction starts with the cis-trans isomerization of the retinal chromophore upon absorption of photons. Despite sharing the common 11-cis-retinal chromophore, rod and cone photoreceptors possess distinct photochemical properties. Thus, a detailed molecular characterization of the chromophore-binding pocket of these receptors is critical to understanding the differences in the photochemistry of vision between rods and cones. Unlike for rhodopsin (Rh), the crystal structures of cone opsins remain to be determined. To obtain insights into the specific chromophore-protein interactions that govern spectral tuning in human visual pigments, here we harnessed the unique binding properties of 11-cis-6-membered-ring-retinal (11-cis- 6mr-retinal) with human blue, green, and red cone opsins. To unravel the specificity of the chromophore-binding pocket of cone opsins, we applied 11-cis-6mr-retinal analog-binding analyses to human blue, green, and red cone opsins. Our results revealed that among the three cone opsins, only blue cone opsin can accommodate the 11-cis-6mr-retinal in its chromophorebinding pocket, resulting in the formation of a synthetic blue pigment (B6mr) that absorbs visible light. A combination of primary sequence alignment, molecular modeling, and mutagenesis experiments revealed the specific amino acid residue 6.48 (Tyr-262 in blue cone opsins and Trp-281 in green and red cone opsins) as a selectivity filter in human cone opsins. Altogether, the results of our study uncover the molecular basis underlying the binding selectivity of 11-cis-6mr-retinal to the cone opsins. [ABSTRACT FROM AUTHOR]

We examined lens and brille transmittance, photoreceptors, visual pigments, and visual opsin gene sequences of viperid snakes with and without infrared-sensing pit organs. Ocular media transmittance was high in both groups. Contrary to previous reports, both small and large single cones occur in pit vipers. Non-pit vipers differ from pit vipers in having a two-tiered retina, but few taxa have been examined for this poorly understood feature. All vipers sampled express rh1, sws1 and lws visual opsin genes. Opsin spectral tuning varies but not in accordance with the presence/absence of pit organs, and not always as predicted from gene sequences. The visual opsin genes were generally under purifying selection, with positive selection at spectral tuning amino acids in RH1 and SWS1 opsins, and at retinal pocket stabilization sites in RH1 or LWS (and without substantial differences between pit and non-pit vipers). A lack of evidence for a sensory trade-off between viperid eyes (in the aspects examined) and pit organs might be explained by the high degree of neural integration of vision and infrared detection; the latter represents an elaboration of an existing sense with addition of a novel sense organ, rather than involving the evolution of a wholly novel sensory system. [ABSTRACT FROM AUTHOR]

Purpose. To evaluate choroidal thickness in patients with coeliac disease (CD) using spectral domain optical coherence tomography (SD-OCT) and to compare the results to normal eyes. Methods. Seventy patients with CD and 70 healthy controls were included in this prospective, comparative study. All participants underwent a complete ophthalmologic evaluation and SD-OCT. Subfoveal, nasal (nasal distance to fovea 500 μm, 1000 μm, and 1500 μm), and temporal (temporal distance to fovea 500 μm, 1000 μm, and 1500 μm) choroidal thickness measurements were performed using SD-OCT. Results. There were no significant differences in sex, ages, and axial lengths between the groups (p=1.0, p=0.601, p=0.314, respectively). The mean choroidal thickness measurements at all predefined measurement point areas were higher in the coeliac group than in the healthy controls (p<0.001). Of all patients with coeliac disease (70 eyes of 70 patients), 64 eyes (84.2%) had uncomplicated pachychoroid (UCP), one eye had pachychoroid pigment epitheliopathy (PPE), and five eyes in the UCP group had PPE in fellow eyes. Conclusion. It is probable that systemic inflammation in coeliac patients causes the enlargement of choroidal vessels and increasing choroidal thickness. PPE, which is believed to be the precursor of central serous chorioretinopathy, can be observed in coeliac patients. [ABSTRACT FROM AUTHOR]

Macular pseudoholes (MPHs) and lamellar macular holes (LMHs) have been recently defined according to spectral domain optical coherence tomography (SD-OCT) criteria. A major feature for differentiating an MPH from an LMH remains the loss of foveal tissue. The anatomy of the foveola is peculiar with the macular pigment (MP) embedded in a very thin layer of tissue underlying the internal limiting membrane and mainly constituted of a specialized group of Müller cells and Henle's fibers. Despite the near microscopic resolution (≈5–7 μm) and the capability to visualize the outer retina in detail, SD-OCT may fail to ascertain whether a very small loss of this foveolar tissue has occurred. Blue-fundus autofluorescence (B-FAF) imaging is useful in this respect because even very small loss of MP can be identified, suggesting a corresponding localized loss of the innermost layers of the foveola. A definition of MP loss would help differentiating an LMH from an MPH where B-FAF imaging will be negative. [ABSTRACT FROM AUTHOR]

The retinal pigment epithelium (RPE) is a specialized monolayer of pigmented cells within the eye that is critical for maintaining visual system function. Diseases affecting the RPE have dire consequences for vision, and the most prevalent of these is atrophic (dry) age-related macular degeneration (AMD), which is thought to result from RPE dysfunction and degeneration. An intriguing possibility for treating RPE degenerative diseases like atrophic AMD is the stimulation of endogenous RPE regeneration; however, very little is known about the mechanisms driving successful RPE regeneration in vivo. Here, we developed a zebrafish transgenic model (rpe65a:nfsB-eGFP) that enabled ablation of large swathes of mature RPE. RPE ablation resulted in rapid RPE degeneration, as well as degeneration of Bruch’s membrane and underlying photoreceptors. Using this model, we demonstrate for the first time that zebrafish are capable of regenerating a functional RPE monolayer after RPE ablation. Regenerated RPE cells first appear at the periphery of the RPE, and regeneration proceeds in a peripheral-to-central fashion. RPE ablation elicits a robust proliferative response in the remaining RPE. Subsequently, proliferative cells move into the injury site and differentiate into RPE. BrdU incorporation assays demonstrate that the regenerated RPE is likely derived from remaining peripheral RPE cells. Pharmacological disruption using IWR-1, a Wnt signaling antagonist, significantly reduces cell proliferation in the RPE and impairs overall RPE recovery. These data demonstrate that the zebrafish RPE possesses a robust capacity for regeneration and highlight a potential mechanism through which endogenous RPE regenerate in vivo. [ABSTRACT FROM AUTHOR]

A four-parameter model of spectral sensitivity curves was developed. Empirical equations were designed for A1- and A2-based visual pigments with the main α-band maximum absorptions (λmax) from 350 nm, near the ultraviolet, up to 635 nm in the far-red part of the spectrum. Subtraction of the α-band from the full absorbance spectrum left a "β-band" described by a λmax-dependent Gaussian equation. Compatibility of our templates with A1- and A2-based spectra was tested on the electroretinographic (ERG-derived) scotopic action spectra recorded in dogfish shark, eel, Prussian carp and perch. To more precisely estimate the accuracy of our model, we compared it with widely used templates for visual pigments. There was almost no difference between the tested models in fitting the above-mentioned spectral data. One of the advantages of our model is that in the fitting of spectral sensitivity data it uses non-transformed wavelengths and the shape of the curve remains the same for a broad range of λmax values. Compared to multiparameter templates of other authors, our model was designed with fewer (four) parameters, which we believe can bring us closer to understanding the true nature of the absorption curve. [ABSTRACT FROM AUTHOR]

Through their unique use of sophisticated laryngeal echolocation bats are considered sensory specialists amongst mammals and represent an excellent model in which to explore sensory perception. Although several studies have shown that the evolution of vision is linked to ecological niche adaptation in other mammalian lineages, this has not yet been fully explored in bats. Recent molecular analysis of the opsin genes, which encode the photosensitive pigments underpinning color vision, have implicated high-duty cycle (HDC) echolocation and the adoption of cave roosting habits in the degeneration of color vision in bats. However, insufficient sampling of relevant taxa has hindered definitive testing of these hypotheses. To address this, novel sequence data was generated for the SWS1 and MWS/LWS opsin genes and combined with existing data to comprehensively sample species representing diverse echolocation types and niches (SWS1 n  = 115; MWS/LWS n  = 45). A combination of phylogenetic analysis, ancestral state reconstruction, and selective pressure analyses were used to reconstruct the evolution of these visual pigments in bats and revealed that although both genes are evolving under purifying selection in bats, MWS/LWS is highly conserved but SWS1 is highly variable. Spectral tuning analyses revealed that MWS/LWS opsin is tuned to a long wavelength, 555–560 nm in the bat ancestor and the majority of extant taxa. The presence of UV vision in bats is supported by our spectral tuning analysis, but phylogenetic analyses demonstrated that the SWS1 opsin gene has undergone pseudogenization in several lineages. We do not find support for a link between the evolution of HDC echolocation and the pseudogenization of the SWS1 gene in bats, instead we show the SWS1 opsin is functional in the HDC echolocator, Pteronotus parnellii. Pseudogenization of the SWS1 is correlated with cave roosting habits in the majority of pteropodid species. Together these results demonstrate that the loss of UV vision in bats is more widespread than was previously considered and further elucidate the role of ecological niche specialization in the evolution of vision in bats. [ABSTRACT FROM AUTHOR]

Abstract To determine the characteristics of the damages of the retinal pigment epithelium (RPE) and photoreceptors of pigmented mice induced by exposure to blue light emitting diode (LED) light, and to determine the mechanisms causing the damages. Exposure to blue LED light for 3 days induced retinal damage, and the characteristics of the damage differed from that induced by white fluorescent light exposure. Ophthalmoscopy showed that blue LED exposure for 3 days induced white spots on the retina, and histological examinations showed materials accumulated at the IS/OS junction of the photoreceptors. The accumulated materials were stained by ionized calcium binding adapter molecule-1 (Iba-1), a marker for macrophages. The debris was also positive for periodic acid-Schiff (PAS). An enlarging the area of RPE was detected just after the blue LED exposure especially around the optic nerve, and this led to a secondary degeneration of the photoreceptors. Exposure of pigmented mice to 3 consecutive days of blue LED light will cause RPE and photoreceptor damage. The damage led to an accumulation of macrophages and drusen-like materials around the outer segments of the photoreceptors. This blue light exposed model may be useful for investigating the pathogenesis of non-exudative age-related macular degeneration. Highlights • Blue light emitting diode (LED) light exposure caused severe damage compared to fluorescent light to pigmented mice. • Repeated blue LED light exposure caused long term thinning of outer nuclear layer and outer segment thickness. • After blue LED-induced retinal damage, macrophage and drusen-like material were accumulated. [ABSTRACT FROM AUTHOR]

Knowledge on the visual spectral sensitivity of a given fish is important for determination of optimal light conditions for improvement of fish rearing in aquaculture. Sutchi catfish (Pangasianodon hypophthalmus Sauvage 1878) is an important freshwater fish species in Southeast Asia. The present study aimed to understand the visual spectral sensitivity of juvenile sutchi catfish through spectrophotometric measurement of the spectral absorbance of wholemounts of retinae. The spectral absorbance curves obtained from the spectrophotometric measurement indicated a parabolic shape. The curves for retinae photo‐bleached with initial flash of blue, green and yellow lights, respectively had a peak at approximately 560 nm, which were the same as the curve for retinae photo‐bleached with broad wavelength light. On the other hand, the curve for retinae photo‐bleached with initial flash of red light had a peak shifted prominently toward shorter light wavelength at approximately 540 nm. This prominent shift of peak implied that the retinae of juvenile sutchi catfish absorb light wavelength of red. Therefore, the present results clearly suggested that juvenile sutchi catfish utilises longer light wavelengths. [ABSTRACT FROM AUTHOR]

According to the sensory drive model, variation in visual properties can lead to diverse female preferences, which in turn results in a range of male nuptial colors by way of sexual selection. However, the cause of variation in visual properties and the mechanism by which variation drives female response to visual signals remain unclear. Here, we demonstrate that both differences in the long-wavelength-sensitive 1 (LWS-1) opsin genotype and the light environment during rearing lead to variation in opsin gene expression. Opsin expression variation affects the visual sensitivity threshold to long wavelengths of light. Moreover, a behavioral assay using digitally modified video images showed that the expression of multiple opsin genes is positively correlated with the female responsiveness to images of males with luminous orange spots. The findings suggest that genetic polymorphisms and light environment in habitats induce variations in opsin gene expression levels. The variations may facilitate variations in visual sensitivity and female responsiveness to male body colors within and among populations. [ABSTRACT FROM AUTHOR]

Purpose. To investigate the incidence and timing of prechoroidal cleft development and its association with visual prognosis in type 3 neovascularization. Methods. This retrospective study included 166 eyes that were diagnosed with type 3 neovascularization. All eyes were treated with antivascular endothelial growth factor therapy. The incidence and timing of prechoroidal cleft development were evaluated. Best-corrected visual acuity (BCVA) at diagnosis and at final follow-up was compared between eyes with (cleft group) and without (no-cleft group) prechoroidal cleft. The incidence of retinal pigment epithelium (RPE) tear and subretinal hemorrhage was also compared between the two groups. Results. During the mean 39.7 ± 18.5 months of follow-up, prechoroidal cleft developed in 37 eyes (22.3%) at an average of 14.6 ± 10.4 months. The BCVA at final follow-up was significantly worse in the cleft group than in the no-cleft group (P=0.024), whereas the difference was not significant at diagnosis (P=0.969). The incidence of RPE tear (P=0.002) and subretinal hemorrhage (P<0.001) was significantly higher in the cleft group. Conclusions. Prechoroidal cleft is a frequently observed finding during the treatment course of type 3 neovascularization. Eyes with prechoroidal cleft are at high risk of RPE tear or subretinal hemorrhage and subsequently associated with poor prognosis. [ABSTRACT FROM AUTHOR]

Purpose. To characterize the spectral-domain optical coherence tomography (SD-OCT) findings of the rhodopsin S334ter transgenic rats (line 4) in relation to the morphologic and electroretinographic features. Materials and Methods. Rhodopsin S334ter transgenic rats (line 4) were employed as a model of retinal degeneration. The Sprague-Dawley (SD) rats were used as a wild-type control. SD-OCT (Micron IV®; Phoenix Research Labs, Pleasanton, CA, USA) was performed on the S334ter rats (line 4) from postnatal days (P) 13−110. The longitudinal changes of the SD-OCT images were analyzed both qualitatively and quantitatively in comparison to those of SD rats. The SD-OCT images were also compared to the histological and electron microscopic findings from examination performed on P 22, 36, and 61. Full field combined rod and cone electroretinography (ERG) was performed and the relationship between the thickness of the retinal sublayers and the amplitudes of the a- and b-waves was further analyzed. Results. The photoreceptor inner and outer segment layer became diffusely hyperreflective in the SD-OCT images of the S334ter rats; these findings were not observed in the SD rats. This hyperreflective change corresponded to the degenerated inner and outer segments and the accumulation of the extracellular vesicles in the interphotoreceptor matrix. Quantitatively, the retinal outer sublayer and the photoreceptor sublayer in the S334ter rats became progressively thinner in comparison to those in the SD rats; the difference was statistically significant. The amplitudes of both the a- and b-waves on ERG were severely deteriorated in the S334ter rats. Discussion. The SD-OCT images in the S334ter rats noninvasively provided information regarding the pathological changes in the photoreceptors and the longitudinal changes of both qualitative and quantitative changes during retinal degeneration in the S334ter rats (line 4). The pathological features of the photoreceptor inner and outer segments can be detected on SD-OCT as diffuse hyperreflective changes in the photoreceptor layer. [ABSTRACT FROM AUTHOR]

Purpose. To evaluate the effect of smoking on the outcome of antivascular endothelial growth factor (VEGF) therapy in patients with neovascular age-related macular degeneration (nAMD). Methods. This retrospective case-control study included 64 eyes in 59 patients with treatment-naïve nAMD. Smoking habits were obtained from hospital records and patient recall. The patients were divided into ever-smokers and never-smokers. The patients were treated with ranibizumab or aflibercept for at least 1 year. Outcome measures were best-corrected visual acuity (BCVA), central retinal thickness (CRT) at the fovea, subfoveal choroidal thickness (SCT), and number of injections received. Results. There were no statistically significant differences in BCVA, CRT, or SCT changes between ever-smokers and never-smokers. The number of injections received was significantly higher in ever-smokers with a history of heavy smokers (never-smokers vs. heavy smokers: 5.3 ± 2.6/year vs. 7.3 ± 2.5/year; P=0.048 and mild smokers vs. heavy smokers: 5.2 ± 2.5/year vs. 7.3 ± 2.5/year; P=0.043). There was no significant difference in the baseline CRT or presence of atrophic retinal pigment epithelium in the fellow eyes of patients with nAMD according to smoking status; however, the baseline CRT in eyes with nAMD was significantly thinner in ever-smokers than in never-smokers (P=0.02). Conclusion. The anti-VEGF therapy was frequently required in nAMD patients with a history of heavy smoking. Heavy smoking could cause poor therapeutic response in nAMD patients. [ABSTRACT FROM AUTHOR]

Background. The flow field of aqueous humor correlates to the stiffness of iris pigment epithelium (IPE) which acts as a wall of posterior chamber. We focus on the variations of IPE stiffness in a rat ocular hypertension (OHT) model, so as to prepare for exploring the mechanism of duration of OHT. Methods. Episcleral venous cauterization (EVC) was applied on one eye of male adult Sprague-Dawley rats to induce chronic high intraocular pressure. According to the duration of OHT (0, 1, 2, 4, and 8 weeks), rats were randomly divided into Gw0, Gw1, Gw2, Gw4, and Gw8. Atomic force microscope (AFM) analysis was applied to test IPE stiffness in three regions: iris root, mid-periphery, and pupillary-margin in each group. Histological changes of IPE were also examined in Gw4 and Gw8. Results. There was an overall growing tendency of IPE stiffness in EVC eye. IPE in EVC eye was significantly stiffer than fellow eye in Gw2, Gw4, and Gw8 (in iris root, mid-periphery, and pupillary-margin, p<0.05). IPE in EVC eye in pupillary-margin was significantly stiffer than iris root in Gw4 and Gw8 (p<0.05). In EVC eye, IPE becomes thinner and IPE cell density decreases. Conclusion. IPE stiffness increases gradually with the duration of chronic high intraocular pressure. [ABSTRACT FROM AUTHOR]

Purpose. Diabetes is known to cause alterations in retinal microvasculature and tissue that progressively lead to visual impairment. Optical coherence tomography (OCT) is useful for assessment of total retinal thickening due to diabetic macular edema (DME). In the current study, we determined associations between visual acuity (VA) and retinal layer thickness, reflectance, and interface disruption derived from enface OCT images in subjects with and without DME. Materials and Methods. Best corrected VA was measured and high-density OCT volume scans were acquired in 149 diabetic subjects. A previously established image segmentation method identified retinal layer interfaces and locations of visually indiscernible (disrupted) interfaces. Enface thickness maps and reflectance images of the nerve fiber layer (NFL), combined ganglion cell and inner plexiform layer (GCLIPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), photoreceptor outer segment layer (OSL), and retinal pigment epithelium (RPE) were generated in the central macular subfield. The associations among VA and retinal layer metrics were determined by multivariate linear regressions after adjusting for covariates (age, sex, race, HbA1c, diabetes type, and duration) and correcting for multiple comparisons. Results. In DME subjects, increased GCLIPL and OPL thickness and decreased OSL thickness were associated with reduced VA. Furthermore, increased NFL reflectance and decreased OSL reflectance were associated with reduced VA. Additionally, increased areas of INL and ONL interface disruptions were associated with reduced VA. In subjects without DME, increased INL thickness was associated with reduced VA, whereas in subjects without DME but with previous antivascular endothelium growth factor treatment, thickening of OPL was associated with reduced VA. Conclusions. Alterations in retinal layer thickness and reflectance metrics derived from enface OCT images were associated with reduced VA with and without presence of DME, suggestive of their potential for monitoring development, progression, and treatment of DME. [ABSTRACT FROM AUTHOR]

This study investigated categorical perception for unique hues in order to establish a relationship between color appearance, color discrimination, and low-level (second-stage) mechanisms. We tested whether pure red, yellow, green, and blue, (unique hues) coincide with troughs, and their transitions (binary hues) with peaks of sensitivity in DKL-space. Results partially confirmed this idea: JNDs demarcated perceptual categories at the binary hues around green, blue and less clearly around yellow, when colors were isoluminant with the background and when accounting for the overall variation of sensitivity by fitting an ellipse. The categorical JND pattern for those three categories was in line with the effect of the second-stage mechanisms. In contrast, the results for unique red, binary red-yellow, and the JNDs for dark colors clearly contradicted categorical perception. There was a JND maximum around the center of red and JNDs strongly decreased away from the center. Although this observation alone would also be in line with categorical perception; unique red was shifted away from the center towards yellow so that unique red was close to the minimum instead of the maximum JND, hence contradicting categorical perception. In addition, we also showed that observers do not adjust unique hues more consistently than binary hues, confirming a previous study. Taken together, our findings suggest that some of the unique hues could be inherent in the early stages of color processing. At the same time, they also raise questions about complex effects of lightness, chroma and instructions on the measurements of JNDs and unique hues. [ABSTRACT FROM AUTHOR]

Physiological, anatomical, and psychophysical evidence points to important differences between visual processing of short-wave cone increments and decrement (S+ and S-) stimuli. The present study uses the pedestal discrimination paradigm to investigate potential differences, using S+ and S- tests presented on (L)ong-wave, (M)edium-wave, S, L+M, L-M, and achromatic pedestals, of both contrast polarities. Results show that high contrast 'purplish' (S+ or -(L+M)) pedestals produce substantially more masking of both S+ and S- tests than 'yellowish' (S- or +(L+M)) pedestals do. The other pedestals produce no masking. These findings suggest greater nonlinearity - either a static nonlinearity or contrast gain control - in the mechanisms responsible for the 'purplish' polarity, likely the S ON pathway. [ABSTRACT FROM AUTHOR]

Drosophila retinal degeneration C (RDGC) is the founding member of the PPEF family of protein phosphatases. RDGC mediates dephosphorylation of the visual pigment rhodopsin and the TRP ion channel. From the rdgC locus, three protein isoforms, termed RDGC-S, -M, and -L, with different N-termini are generated. Due to fatty acylation, RDGC-M and -L are attached to the plasma membrane while RDGC-S is soluble. To assign physiological roles to these RDGC isoforms, we constructed flies that express various combinations of RDGC protein isoforms. Expression of the RDGC-L isoform alone did not fully prevent rhodopsin hyperphosphorylation and resulted in impaired photoreceptor physiology and in decelerated TRP dephosphorylation at Ser936. However, expression of RDGC-L alone as well as RDGC-S/M was sufficient to prevent degeneration of photoreceptor cells which is a hallmark of the rdgC null mutant. Membrane-attached RDGC-M displayed higher activity of TRP dephosphorylation than the soluble isoform RDGC-S. Taken together, in vivo activities of RDGC splice variants are controlled by their N-termini. [ABSTRACT FROM AUTHOR]