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Purpose: To evaluate clinical and demographic features of Vogt-Kayanagi-Harada disease (VKH) disease in Turkish patients and compare them with previously published data. Methods: Demographic and clinical features of 32 patients diagnosed as VKH in a tertiary referral center were retrospectively reviewed. Results: The mean age at presentation was 33.6 ± 10.4 years. Seventy-five percent of the patients were female and 62.5% of the patients presented during the last 2 years. The disease was complete in 31.2%, incomplete in 50%, and probable in 18.8% of the patients. The clinical course was acute in 50%, chronic recurrent in 34.4%, and chronic in 15.6%. The most common findings were bilateral serous retinal detachment ± papillitis in acute cases and retinal pigment epithelial changes of the macula in chronic cases. Conclusions: Although rare in Turkey, VKH disease seems to have increased during the last few years. The disease is incomplete and acute in half of the patients and has a quite good visual prognosis. [ABSTRACT FROM AUTHOR]

Background Synonymous codon usage can affect many cellular processes, particularly those associated with translation such as polypeptide elongation and folding, mRNA degradation/stability, and splicing. Highly expressed genes are thought to experience stronger selection pressures on synonymous codons. This should result in codon usage bias even in species with relatively low effective population sizes, like mammals, where synonymous site selection is thought to be weak. Here we use phylogenetic codon-based likelihood models to explore patterns of codon usage bias in a dataset of 18 mammalian rhodopsin sequences, the protein mediating the first step in vision in the eye, and one of the most highly expressed genes in vertebrates. We use these patterns to infer selection pressures on key translational mechanisms including polypeptide elongation, protein folding, mRNA stability, and splicing. Results Overall, patterns of selection in mammalian rhodopsin appear to be correlated with post-transcriptional and translational processes. We found significant evidence for selection at synonymous sites using phylogenetic mutation-selection likelihood models, with C-ending codons found to have the highest relative fitness, and to be significantly more abundant at conserved sites. In general, these codons corresponded with the most abundant tRNAs in mammals. We found significant differences in codon usage bias between rhodopsin loops versus helices, though there was no significant difference in mean synonymous substitution rate between these motifs. We also found a significantly higher proportion of GC-ending codons at paired sites in rhodopsin mRNA secondary structure, and significantly lower synonymous mutation rates in putative exonic splicing enhancer (ESE) regions than in non-ESE regions. Conclusions By focusing on a single highly expressed gene we both distinguish synonymous codon selection from mutational effects and analytically explore underlying functional mechanisms. Our results suggest that codon bias in mammalian rhodopsin arises from selection to optimally balance high overall translational speed, accuracy, and proper protein folding, especially in structurally complicated regions. Selection at synonymous sites may also be contributing to mRNA stability and splicing efficiency at exonic-splicing-enhancer (ESE) regions. Our results highlight the importance of investigating highly expressed genes in a broader phylogenetic context in order to better understand the evolution of synonymous substitutions. [ABSTRACT FROM AUTHOR]

In mammals, a subset of retinal ganglion cells (RGCs) expresses the photopigment melanopsin, which renders them intrinsically photosensitive (ipRGCs). These ipRGCs mediate various non-image-forming visual functions such as circadian photoentrainment and the pupillary light reflex (PLR). Melanopsin phototransduction begins with activation of a heterotrimeric G protein of unknown identity. Several studies of melanopsin phototransduction have implicated a G-protein of the Gq/11 family, which consists of Gna11, Gna14, Gnaq and Gna15, in melanopsin-evoked depolarization. However, the exact identity of the Gq/11 gene involved in this process has remained elusive. Additionally, whether Gq/11 G-proteins are necessary for melanopsin phototransduction in vivo has not yet been examined. We show here that the majority of ipRGCs express both Gna11 and Gna14, but neither Gnaq nor Gna15. Animals lacking the melanopsin protein have well-characterized deficits in the PLR and circadian behaviors, and we therefore examined these non-imaging forming visual functions in a variety of single and double mutants for Gq/11 family members. All Gq/11 mutant animals exhibited PLR and circadian behaviors indistinguishable from WT. In addition, we show persistence of ipRGC light-evoked responses in Gna11−/−; Gna14−/− retinas using multielectrode array recordings. These results demonstrate that Gq, G11, G14, or G15 alone or in combination are not necessary for melanopsin-based phototransduction, and suggest that ipRGCs may be able to utilize a Gq/11-independent phototransduction cascade in vivo. [ABSTRACT FROM AUTHOR]

New World monkeys exhibit prominent colour vision variation due to allelic polymorphism of the long-to-middle wavelength (L/M) opsin gene. The known spectral variation of L/M opsins in primates is broadly determined by amino acid composition at three sites: 180, 277 and 285 (the 'three-sites' rule). However, two L/M opsin alleles found in the black-handed spider monkeys ( Ateles geoffroyi) are known exceptions, presumably due to novel mutations. The spectral separation of the two L/M photopigments is 1.5 times greater than expected based on the 'three-sites' rule. Yet the consequence of this for the visual ecology of the species is unknown, as is the evolutionary mechanism by which spectral shift was achieved. In this study, we first examine L/M opsins of two other Atelinae species, the long-haired spider monkeys ( A. belzebuth) and the common woolly monkeys ( Lagothrix lagotricha). By a series of site-directed mutagenesis, we show that a mutation Y213D (tyrosine to aspartic acid at site 213) in the ancestral opsin of the two alleles enabled N294K, which occurred in one allele of the ateline ancestor and increased the spectral separation between the two alleles. Second, by modelling the chromaticity of dietary fruits and background leaves in a natural habitat of spider monkeys, we demonstrate that chromatic discrimination of fruit from leaves is significantly enhanced by these mutations. This evolutionary renovation of L/M opsin polymorphism in atelines illustrates a previously unappreciated dynamism of opsin genes in shaping primate colour vision. [ABSTRACT FROM AUTHOR]

This study reports that the spontaneous 50-fold activation of rhodopsin gene transcription, observed in cultured retinal precursors from 13-day chicken embryo, relies on a Ca2+-dependent mechanism. Activation of a transiently transfected rhodopsin promoter (luciferase reporter) in these cells was inhibited (60%) by cotransfection of a dominant-negative form of the cAMP-responsive element-binding protein. Both rhodopsin promoter activity and rhodopsin mRNA accumulation were blocked by Ca2+/calmodulin-dependent kinase II inhibitors, but not by protein kinase A inhibitors, suggesting a role of Ca2+ rather than cAMP. This was confirmed by the inhibitory effect of general and T-type selective Ca2+ channel blockers. Oscillations in Ca2+ fluorescence (Fluo8) could be observed in 1/10 cells that activated the rhodopsin promoter (DsRed reporter). A robust and reversible inhibition of rhodopsin gene transcription by ZD7288 indicated a role of hyperpolarization-activated channels (HCN). Cellular localization and developmental expression of HCN1 were compatible with a role in the onset of rhodopsin gene transcription. Together, the data suggest that the spontaneous activation of rhodopsin gene transcription in cultured retinal precursors results from a signaling cascade that involves the pacemaker activity of HCN channels, the opening of voltage-gated Ca2+-channels, activation of Ca2+/calmodulin-dependent kinase II and phosphorylation of cAMP-responsive element-binding protein. [ABSTRACT FROM AUTHOR]

Retinal ganglion cells transmit the visual signal from the retina to the brain. We have previously shown that the activator protein 2 (AP-2)δ (TFAP2D) transcription factor is expressed in one third of ganglion cells in developing retina suggesting a specialized role for these AP-2δ-expressing cells. Here, we address the role of AP-2δ in retina by in ovo electroporation of RCAS/AP-2δ retroviral constructs into the eyes of chick embryos at day 2 of gestation. Ectopic expression of AP-2δ does not affect lineage differentiation in the developing retina. However, immunostaining of retinal tissue with markers associated with axonal growth such as growth-associated protein 43 and polysialic acid-neural cell adhesion molecule (PSA-NCAM) demonstrates axonal misrouting and abnormal axonal bundling. Treatment of AP-2δ-misexpressing retinal cell cultures with endoneuraminidase, an enzyme that removes PSA from NCAM, decreases AP-2δ-induced axonal bundling. Our data suggest a role for AP-2δ in polysialylation of NCAM, with ectopic expression of AP-2δ resulting in premature bundling of emerging axons and misrouting of axons. We propose that expression of AP-2δ in a subset of ganglion cells contributes to the fine-tuning of axonal growth in the developing retina. [ABSTRACT FROM AUTHOR]

The article describes the case of a 71-year-old male who complained of blurred vision and who was diagnosed with an acquired vitelliform lesion overlying a drusenoid pigment epithelial detachment (PED). The topics discussed include the patient's case history, the complications of age-related macular degeneration, and the migration of drusenoid material through a spontaneous retinal pigment epithelial tear.

Summary: 11-cis-retinal acts as an inverse agonist stabilizing the inactive conformation of visual pigments, and upon photoactivation, it isomerizes to all-trans-retinal, initiating signal transduction. We have analyzed opsin regeneration with retinal analogs for rhodopsin and red cone opsin. We find differential binding of the analogs to the receptors after photobleaching and a dependence of the binding kinetics on the oligomerization state of the protein. The results outline the sensitivity of retinal entry to the binding pocket of visual receptors to the specific conformation adopted by the receptor and by the molecular architecture defined by specific amino acids in the binding pocket and the retinal entry site, as well as the topology of the retinal analog. Overall, our findings highlight the specificity of the ligand-opsin interactions, a feature that can be shared by other G-protein-coupled receptors. [ABSTRACT FROM AUTHOR]

Background: the xanthophylls lutein (L) and zeaxanthin (Z) exist in relatively high concentration in multiple central nervous tissues (e.g. cortex and neural retina). L + Z in macula (i.e. macular pigment, MP) are thought to serve multiple functions, including protection and improvement of visual performance. Also, L + Z in the macula are related to L + Z in the cortex.Objective: to determine whether macular pigment optical density (MPOD, L + Z in the macula) is related to cognitive function in older adults.Methods: participants were older adults (n = 108, 77.6 ± 2.7 years) sampled from the age-related maculopathy ancillary study of the Health Aging and Body Composition Study (Memphis, TN, USA). Serum carotenoids were measured using high performance liquid chromatography. MPOD was assessed using heterochromatic flicker photometry. Eight cognitive tests designed to evaluate several cognitive domains including memory and processing speed were administered. Partial correlation coefficients were computed to determine whether cognitive measures were related to serum L + Z and MPOD.Results: MPOD levels were significantly associated with better global cognition, verbal learning and fluency, recall, processing speed and perceptual speed, whereas serum L + Z was significantly related to only verbal fluency.Conclusion: MPOD is related to cognitive function in older people. Its role as a potential biomarker of cognitive function deserves further study. [ABSTRACT FROM AUTHOR]

Differential rhodopsin gene expression within specialized R7 photoreceptor cells divides the retinas of Aedes aegypti and Anopheles gambiae mosquitoes into distinct domains. The two species express the rhodopsin orthologs Aaop8 and Agop8, respectively, in a large subset of these R7 photoreceptors that function as ultraviolet receptors. We show here that a divergent subfamily of mosquito rhodopsins, Aaop10 and Agop10, is coexpressed in these R7 photoreceptors. The properties of the A. aegypti Aaop8 and Aaop10 rhodopsins were analyzed by creating transgenic Drosophila expressing these rhodopsins. Electroretinogram recordings, and spectral analysis of head extracts, obtained from the Aaop8 strain confirmed that Aaop8 is an ultravioletsensitive rhodopsin. Aaop10 was poorly expressed and capable of eliciting only small and slow light responses in Drosophila photoreceptors, and electroretinogram analysis suggested that it is a long-wavelength rhodopsin with a maximal sensitivity near 500 nm. Thus, coexpression of Aaop10 rhodopsin with Aaop8 rhodopsin has the potential to modify the spectral properties of mosquito ultraviolet receptors. Retention of Op10 rhodopsin family members in the genomes of Drosophila species suggests that this rhodopsin family may play a conserved role in insect vision. [ABSTRACT FROM AUTHOR]

Isorhodopsin is the visual pigment analogue of rhodopsin. It shares the same opsin environment but it embeds 9- cis retinal instead of 11- cis. Its photoisomerization is three times slower and less effective. The mechanistic rationale behind this observation is revealed by combining high-level quantum-mechanical/molecular-mechanical simulations with ultrafast optical spectroscopy with sub-20 fs time resolution and spectral coverage extended to the near-infrared. Whereas in rhodopsin the photoexcited wavepacket has ballistic motion through a single conical intersection seam region between the ground and excited states, in isorhodopsin it branches into two competitive deactivation pathways involving distinct conical intersection funnels. One is rapidly accessed but unreactive. The other is slower, as it features extended steric interactions with the environment, but it is productive as it follows forward bicycle pedal motion. [ABSTRACT FROM AUTHOR]

An important component of the cone photoreceptors of bird eyes is the oil droplets located in front of the visual-pigment-containing outer segments. The droplets vary in colour and are transparent, clear, pale or rather intensely yellow or red owing to various concentrations of carotenoid pigments. Quantitative modelling of the filter characteristics using known carotenoid pigment spectra indicates that the pigments' absorption spectra are modified by the high concentrations that are present in the yellow and red droplets. The high carotenoid concentrations not only cause strong spectral filtering but also a distinctly increased refractive index at longer wavelengths. The oil droplets therefore act as powerful spherical microlenses, effectively channelling the spectrally filtered light into the photoreceptor's outer segment, possibly thereby compensating for the light loss caused by the spectral filtering. The spectral filtering causes narrow-band photoreceptor spectral sensitivities, which are well suited for spectral discrimination, especially in birds that have feathers coloured by carotenoid pigments. [ABSTRACT FROM AUTHOR]

Most vertebrate retinas contain two types of photoreceptor cells, rods and cones, which show different photoresponses to mediate scotopic and photopic vision, respectively. These cells contain different types of visual pigments, rhodopsin and cone visual pigments, respectively, but little is known about the molecular properties of cone visual pigments under physiological conditions, making it difficult to link the molecular properties of rhodopsin and cone visual pigments with the differences in photoresponse between rods and cones. Here we prepared bovine and mouse rhodopsin (bvRh and mRh) and chicken and mouse green-sensitive cone visual pigments (cG and mG) embedded in nanodiscs and applied time-resolved fluorescence spectroscopy to compare their Gt activation efficiencies. Rhodopsin exhibited greater Gt activation efficiencies than cone visual pigments. Especially, the Gt activation efficiency of mRh was about 2.5-fold greater than that of mG at 37 °C, which is consistent with our previous electrophysiological data of knock-in mice. Although the active state (Meta-II) was in equilibrium with inactive states (Meta-I and Meta-III), quantitative determination of Meta-II in the equilibrium showed that the Gt activation efficiency per Meta-II of bvRh was also greater than those of cG and mG. These results indicated that efficient Gt activation by rhodopsin, resulting from an optimized active state of rhodopsin, is one of the causes of the high amplification efficiency of rods. [ABSTRACT FROM AUTHOR]

Comparative modeling and ab initio multiconfigurational quantum chemistry are combined to investigate the reactivity of the human nonvisual photoreceptor melanopsin. It is found that both the thermal and photochemical isomerization of the melanopsin 11-cis retinal chromophore occur via a space-saving mechanism involving the unidirectional, counterclockwise twisting of the =C11H-C12H= moiety with respect to its Lys340-linked frame as proposed byWarshel for visual pigments [Warshel A (1976) Nature 260 (5553):679-683]. A comparison with the mechanisms documented for vertebrate (bovine) and invertebrate (squid) visual photoreceptors shows that such a mechanism is not affected by the diversity of the three chromophore cavities. Despite such invariance, trajectory computations indicate that although all receptors display less than 100 fs excited state dynamics, human melanopsin decays from the excited state ∼40 fs earlier than bovine rhodopsin. Some diversity is also found in the energy barriers controlling thermal isomerization. Human melanopsin features the highest computed barrier which appears to be ∼2.5 kcal mol-1 higher than that of bovine rhodopsin. When assuming the validity of both the reaction speed/quantum yield correlation discussed byWarshel,Mathies and coworkers [Weiss RM,Warshel A (1979) J AmChemSoc 101:6131-6133; Schoenlein RW, Peteanu LA, Mathies RA, Shank CV (1991) Science 254(5030):412-415] and of a relationship between thermal isomerization rate and thermal activation of the photocycle, melanopsin turns out to be a highly sensitive pigment consistent with the low number of melanopsincontaining cells found in the retina and with the extraretina location of melanopsin in nonmammalian vertebrates. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the molecular mechanisms, functions and structures of microbial and animal rhodopsins. The variations in the molecular mechanisms involved in the synthesis of microbial and animal rhodopsins are outlined. The applications of rhodopsins in neuroscience and optogenetics are discussed.

Background: A common haplotype in the gene for the regulator of the alternative pathway of complement activation factor H has been linked to individual predisposition to age- related macular degeneration (AMD). Methods: In this study, retinal pigment epithelial (RPE) cells, i.e. immortalized ARPE-19 as well as primary human RPE cells, were investigated for expression of factor H and FHL-1 by immunohistochemistry and in situ hybridization analysis. Results: Factor H and the alternative spliced product FHL-1 are expressed in RPE cells, i.e. in immortalized ARPE-19 and primary human RPE cells. Factor H and FHL-1 expression was induced in a dose-dependent manner in ARPE-19 cells upon treatment with the inflammatory marker interleukin-6 (IL-6). In situ hybridization experiments confirmed an elevated expression rate of the factor H gene in IL-6-treated ARPE-19 cells. AMD is characterized by complement-associated inflammatory processes in the retina. Thus, local synthesis of complement regulators affects the protection of retinal cells and may be involved in the pathogenesis at the RPE-choroid interface. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Our previous study suggested the presence of a novel cone specific redox reaction that generates 11-cis-retinal from11-cis-retinol in the carp retina. This reaction is unique in that 1) both 11-cis-retinol and all-trans-retinal were required to produce 11-cis-retinal; 2) together with 11-cis-retinal, all-trans-retinol was produced at a 1:1 ratio; and 3) the addition of enzyme cofactors such as NADP(H) was not necessary. This reaction is probably part of the reactions in a cone-specific retinoid cycle required for cone visual pigment regeneration with the use of 11-cis-retinol supplied from Müller cells. In this study, using purified carp cone membrane preparations, we first confirmed that the reaction is a redox-coupling reaction between retinals and retinols. We further examined the substrate specificity, reaction mechanism, and subcellular localization of this reaction. Oxidation was specific for 11-cis-retinol and 9-cis-retinol. In contrast, reduction showed low specificity: many aldehydes, including all-trans-, 9-cis-, 11-cis-, and 13-cis-retinals and even benzaldehyde, supported the reaction. On the basis of kinetic studies of this reaction (aldehyde-alcohol redox-coupling reaction), we found that formation of a ternary complex of a retinol, an aldehyde, and a postulated enzyme seemed to be necessary, which suggested the presence of both the retinol- and aldehydebinding sites in this enzyme. A subcellular fractionation study showed that the activity is present almost exclusively in the cone inner segment.These results suggest the presence of an effective production mechanism of 11-cis-retinal in the cone inner segment to regenerate visual pigment. [ABSTRACT FROM AUTHOR]

Background One of the most striking features of avian vision is the variation in spectral sensitivity of the short wavelength sensitive (SWS1) opsins, which can be divided into two sub-types: violetand UV- sensitive (VS & UVS). In birds, UVS has been found in both passerines and parrots, groups that were recently shown to be sister orders. While all parrots are thought to be UVS, recent evidence suggests some passerine lineages may also be VS. The great bowerbird (Chlamydera nuchalis) is a passerine notable for its courtship behaviours in which males build and decorate elaborate bower structures. Results The great bowerbird SWS1 sequence possesses an unusual residue combination at known spectral tuning sites that has not been previously investigated in mutagenesis experiments. In this study, the SWS1 opsin of C. nuchalis was expressed along with a series of spectral tuning mutants and ancestral passerine SWS1 pigments, allowing us to investigate spectral tuning mechanisms and explore the evolution of UV/violet sensitivity in early passerines and parrots. The expressed C. nuchalis SWS1 opsin was found to be a VS pigment, with a λmax of 403 nm. Bowerbird SWS1 mutants C86F, S90C, and C86S/S90C all shifted λmax into the UV, whereas C86S had no effect. Experimentally recreated ancestral passerine and parrot/passerine SWS1 pigments were both found to be VS, indicating that UV sensitivity evolved independently in passerines and parrots from a VS ancestor. Conclusions Our mutagenesis studies indicate that spectral tuning in C. nuchalis is mediated by mechanisms similar to those of other birds. Interestingly, our ancestral sequence reconstructions of SWS1 in landbird evolution suggest multiple transitions from VS to UVS, but no instances of the reverse. Our results not only provide a more precise prediction of where these spectral sensitivity shifts occurred, but also confirm the hypothesis that birds are an unusual exception among vertebrates where some descendants re-evolved UVS from a violet type ancestor. The re-evolution of UVS from a VS type pigment has not previously been predicted elsewhere in the vertebrate phylogeny. [ABSTRACT FROM AUTHOR]

The potential for color vision in elasmobranchs has been studied in detail; however, a high degree of variation exists among the group. Evidence for ultraviolet (UV) vision is lacking, despite the presence of UV vision in every other vertebrate class. An integrative physiological approach was used to investigate color and ultraviolet vision in cownose rays and yellow stingrays, two batoids that inhabit different spectral environments. Both species had peaks in UV, short, medium, and long wavelength spectral regions in dark-, light-, and chromatic-adapted electroretinograms. Although no UV cones were found with microspectrophotometric analysis, both rays had multiple cone visual pigments with λmax at 470 and 551 nm in cownose rays ( Rhinoptera  bonasus) and 475, 533, and 562 nm in yellow stingrays ( Urobatis  jamaicensis). The same analysis demonstrated that both species had rod λmax at 500 and 499 nm, respectively. The lens and cornea of cownose rays maximally transmitted wavelengths greater than 350 nm and greater than 376 nm in yellow stingrays. These results support the potential for color vision in these species and future investigations should reveal the extent to which color discrimination is significant in a behavioral context. [ABSTRACT FROM AUTHOR]

Human X-linked blue-cone monochromacy (BCM), a disabling congenital visual disorder of cone photoreceptors, is a candidate disease for gene augmentation therapy. BCM is caused by either mutations in the red ( OPN1LW) and green ( OPN1MW) cone photoreceptor opsin gene array or large deletions encompassing portions of the gene array and upstream regulatory sequences that would predict a lack of red or green opsin expression. The fate of opsin-deficient cone cells is unknown. We know that rod opsin null mutant mice show rapid postnatal death of rod photoreceptors. Using in vivo histology with high-resolution retinal imaging, we studied a cohort of 20 BCM patients (age range 5-58) with large deletions in the red/green opsin gene array. Already in the first years of life, retinal structure was not normal: there was partial loss of photoreceptors across the central retina. Remaining cone cells had detectable outer segments that were abnormally shortened. Adaptive optics imaging confirmed the existence of inner segments at a spatial density greater than that expected for the residual blue cones. The evidence indicates that human cones in patients with deletions in the red/green opsin gene array can survive in reduced numbers with limited outer segment material, suggesting potential value of gene therapy for BCM. [ABSTRACT FROM AUTHOR]

Intraspecific differences in retinal physiology have been demonstrated in several vertebrate taxa and are often subject to adaptive evolution. Nonetheless, such differences are currently unknown in birds, despite variations in habitat, behaviour and visual stimuli that might influence spectral sensitivity. The parrot Platycercus elegans is a species complex with extreme plumage colour differences between (and sometimes within) subspecies, making it an ideal candidate for intraspecific differences in spectral sensitivity. Here, the visual pigments of P. elegans were fully characterised through molecular sequencing of five visual opsin genes and measurement of their absorbance spectra using microspectrophotometry. Three of the genes, LWS, SW1 and SWS2, encode for proteins similar to those found in other birds; however, both the RH1 and RH2 pigments had polypeptides with carboxyl termini of different lengths and unusual properties that are unknown previously for any vertebrate visual pigment. Specifically, multiple RH2 transcripts and protein variants (short, medium and long) were identified for the first time that are generated by alternative splicing of downstream coding and non-coding exons. Our work provides the first complete characterisation of the visual pigments of a parrot, perhaps the most colourful order of birds, and moreover suggests more variability in avian eyes than hitherto considered. [ABSTRACT FROM AUTHOR]

Abstract: To study growth and development of ocular tissues, gene expression patterns in normal human fetal versus adult eyes were compared. Human retina/retinal pigment epithelium, choroid, sclera, optic nerve* and cornea* tissues were dissected from fetal (24 week gestational age) (N = 9; *N = 6), and adult (N = 6) normal donor eyes. The Illumina® whole genome expression microarray platform was used to assess differential expression. Statistical significance for all comparisons was determined using the Benjamin and Hochberg False Discovery Rate (FDR, 5%). Significant gene expression fold changes > 1.5 were found in adult versus fetal retina/RPE (N = 1185), choroid (N = 6446), sclera (N = 1349), and cornea (N = 3872), but not optic nerve. Genes showing differential expression were assessed using Ingenuity Pathway Analysis (IPA) for enriched functions and canonical pathways. In all tissues, development, cell death/growth, cancer functions, and signaling canonical pathways were enriched. There was also a general trend of down-regulation of collagen genes in adult tissues. [Copyright &y& Elsevier]

Highlights: [•] Carp cone visual pigments were expressed and their absorption spectra were measured. [•] Green pigment was phosphorylated by GRK7 more efficiently than blue pigment. [•] Different photoresponse kinetics may be due to the different phosphorylation rates. [ABSTRACT FROM AUTHOR]

Background: The correlation between histologically identified regeneration of retinal pigment epithelium (RPE) and functional outcome measured by multifocal electroretinography (mfERG) following surgical debridement is examined in a porcine model. In humans, visual acuity is reduced in diseases with RPE loss such as RPE tears and geographic atrophy. Hypopigmented RPE is known to cover the lesion after RPE debridement in the pig, but it is unclear whether this leads to a return of photoreceptor function. Methods: RPE debridement was performed in ten pigs by vitrectomy and retinotomy, and by brushing the Bruch's membrane with a silicone catheter. Immediately following surgery (baseline) and after 2 and 6 weeks respectively, the animals were examined by mfERG, fundus photographs (FPs), fluorescein angiograms (FAs), and histopathology. Results: The mfERG P1 amplitude was decreased 2 weeks (T) after surgery; it returned to baseline 6 weeks (T) after surgery. FPs, FAs, and histology showed partial repopulation of Bruch's membrane by hypopigmented RPE cells and atrophied outer segments at T At T, normally pigmented RPE cells were identified, and the photoreceptor layer was restored. Conclusion: This is the first study to show that the histological regeneration of hypopigmented RPE correlates to a return of the retinal function, measured by mfERG. [ABSTRACT FROM AUTHOR]

Background: Retinal tacks, first developed for the treatment of complex retinal detachments, have more recently been used for the fixation of epiretinal electrode arrays as part of implanted visual prostheses. Here, we report on the clinical experience of extracting four such tacks after chronic implantation. The ability to safely extract retinal tacks ensures that epiretinal devices can be repositioned or removed if necessary. Methods: Custom-built, titanium alloy retinal tacks were mechanically removed from the posterior coats after prolonged implantation (up to 19 months). The resulting wound was characterized by clinical evaluation, fundus photography, and fluorescein angiography while being monitored for stability over time. The wounds were also compared to earlier published reports of the healing response around retinal tacks in human subjects. Results: Tack extraction was accomplished successfully, without complication, in all four subjects. The wound site was readily identified by pale scar tissue. No change in the wound size or appearance was noted over many months of post-operative observation (up to 22 months after explant). No adverse effects on overall ocular health were detected. Conclusion: Extraction of retinal tacks from subjects implanted with epiretinal prostheses can be performed without significant complication. The long-term healing response appears to be stable and localized in eyes afflicted with retinitis pigmentosa or choroideremia. There was also minimal, if any, impact on the local circulatory system. These cases suggest that the use of retinal tacks for anchoring epiretinal visual prostheses does not preclude safe repositioning or removal of the device more than a year after implant. [ABSTRACT FROM AUTHOR]

Combined hamartoma of the retina and retinal pigment epithelium (CHRRPE) is a rare and benign retinal lesion. Because it may be misdiagnosed as a malignant melanoma of the choroid or retinoblastoma, the differential diagnosis is very important. In this study, clinical and optical coherence tomographic (OCT) characteristics of four cases with CHRRPE are presented and the differential diagnosis is discussed. In all of the eyes, a grey, elevated retinal lesion was detected clinically. Also OCT showed hyper-reflecting retinal elevation with underlying hypo-reflecting shadow due to the dense fibrous tissue or epiretinal membrane. It was concluded that OCT findings could support the clinical observations in the diagnosis of CHRRPE. [ABSTRACT FROM AUTHOR]

Summary: Humans rely on the fovea, the small region of the retina where receptors are most densely packed, for seeing fine spatial detail. Outside the fovea, it is well established that a variety of visual functions progressively decline with eccentricity [1–5]. In contrast, little is known about how vision varies within the central fovea, as incessant microscopic eye movements prevent isolation of adjacent foveal locations [6–8]. Using a new method for restricting visual stimulation to a selected retinal region, we examined the discrimination of fine patterns at different eccentricities within the foveola. We show that high-acuity judgments are impaired when stimuli are presented just a few arcminutes away from the preferred retinal locus of fixation. Furthermore, we show that this dependence on eccentricity is normally counterbalanced by the occurrence of precisely directed microsaccades, which bring the preferred fixation locus onto the stimulus. Thus, contrary to common assumptions, vision is not uniform within the foveola, but targeted microscopic eye movements compensate for this lack of homogeneity. Our results reveal that microsaccades, like larger saccades, enable examination of the stimulus at a finer level of detail and suggest that a reduced precision in oculomotor control may be responsible for the visual acuity impairments observed in various disorders. [ABSTRACT FROM AUTHOR]

Aims To describe retinal and choroidal changes in acute and quiescent central serous chorioretinopathy (CSC) observed with 'En face' spectral domain optical coherence tomography (SD OCT) combined with enhanced-depth imaging (EDI). Methods A prospective and descriptive study at the Rothschild Ophthalmologic Foundation (Paris, France) between September 2011 and February 2012. Eyes with a clinical diagnosis of CSC were examined using SD OCT with EDI, fluorescein and indocyanine green angiography. 3D reconstruction of 197 transverse sections with SD OCT, spaced of 30 μ, provided a virtual macular brick through which 496 sections in the coronal plane resulted in a C-scan or En face OCT image. Results 23 of 29 eyes (79%) had serous retinal detachment (all active CSC) and 22 had pigment epithelial detachment (75%). Pigment epithelial hyperplasia was visualised in nine eyes (31%). Posterior cystoid retinal degenerations were present in five eyes (17%). The mean choroidal thickness was 491.5 μ. In 11 eyes (38%), En face OCT showed multiple hyper reflective points located at the level of the choriocapillary layer and choroidal cavitations were found in two patients. Conclusions En face OCT imaging using SD OCT is an easy, reproducible, non-invasive and effective tool to understand choroidal changes in acute and quiescent CSCR. It provides complementary morphological information, describes new semiological entities and might substitute other exams in the future. [ABSTRACT FROM AUTHOR]

Abstract: Disturbances in the retinal vascular supply are involved in the pathophysiology of the most frequent diseases causing visual impairment and blindness in the Western World. These diseases are diagnosed by noting how morphological lesions in the retina vary in shape, size, location and dynamics, and subsequently concluding the presence of a specific disease entity. This diagnostic approach can be used to identify the site of a retinal vascular occlusion, to assess whether retinal diseases are primarily due to changes in the larger retinal vessels or the microcirculation, and to differentiate the relative involvement of the choroidal and the retinal vascular systems. However, a number of morphological manifestations of retinal vascular disease cannot presently be related to the underlying pathophysiology. The review concludes that there is a need for developing new methods for assessing vascular structure and function in the ciliary vascular system supplying the choroid and the optic nerve head. Presently, the study of these structures relies on imaging techniques with limited penetration and resolution into the tissue. Secondly, there is a need for studying oscillations in retinal vascular function occurring within days to weeks, and for studying regional manifestations of retinal vascular disease. This may constitute the basis for future research in retinal vascular pathophysiology and for the development of new treatment modalities to reduce blindness secondary to retinal vascular disease. [Copyright &y& Elsevier]

Background and purpose In recent years a possible non-motor involvement of the nervous system in amyotrophic lateral sclerosis ( ALS) has come into the focus of research and has been investigated by numerous techniques. Optical coherence tomography ( OCT) - with its potential to reveal neuroaxonal retinal damage - may be an appropriate tool to investigate whether the anterior visual pathway is involved. Our aim was to determine whether OCT-based measures of retinal nerve fiber layer, ganglion cell layer, inner nuclear layer and outer nuclear layer thickness are abnormal in ALS, or correlated with disease severity. Methods Seventy-six ALS patients (144 eyes) and 54 healthy controls (108 eyes; HCs) were examined with OCT, including automated intraretinal macular segmentation. ALS disease severity was determined with the Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised. Results There was no significant difference between ALS patients and HCs in any of the examined OCT measures. Moreover, OCT parameters showed no correlation with clinical measures of disease severity. Conclusions These findings indicate that involvement of the anterior visual pathway is not one of the non-motor manifestations of ALS. [ABSTRACT FROM AUTHOR]

This article presents the research of relationship between the effect of retinal localized chromatic adaptation, the standard rendering methods, and perception of desaturated achromatic reproductions. Within the research, adaptations on three types of adaptation forms at times of 5, 10, and 15 min are performed. To define the impact of the effect, the samples for visual evaluation - the evaluation of the effect of retinal localized chromatic adaptation - are printed by using the gray balance phenomenon: with certain samples, the saturation of colors for which the adaptation is performed is made higher. The research results show the existence of correlation between the researched parameters and a need for further research and description of psychophysical effects in processes of graphic reproductions. © 2012 Wiley Periodicals, Inc. Col Res Appl, 38, 277-283, 2013 [ABSTRACT FROM AUTHOR]

Visual pigments have a conserved phenylalanine in transmembrane helix 5 located near the β-ionone ring of the retinal chromophore. Site-directed mutants of this residue (F207) in a short-wavelength sensitive visual pigment (VCOP) were studied using UV--visible spectroscopy to investigate its role in photosensitivity and formation of the light-activated state. The side chain is important for pigment formation: VCOPF207A, VCOPF207L, VCOPF207M, and VCOPF207W substitutions all bound 11-ciss-retinal and formed a stable visual pigment, while VCOPF207V, VCOPF207S, VCOPF207T, and VCOPF207Y, substitutions do not. The extinction coefficients of all pigments are close, ranging between 35800 and 45600 M-1 cm-1. Remarkably, the mutants exhibit an up to 5-fold reduction in photosensitivity and also abnormal photobleaching behavior. One mutant, VCOPF207A forms an isomeric composition of the retinal chromophore after illuminationcomparable to that of wild-type VCOP yet does not release the all-trans-retinal chromophore. These findings suggest that the conserved F207 residue is important for a normal photoactivation pathway, formation of the active conformation and the exit of all-trans-retinal from the chromophore-binding pocket. [ABSTRACT FROM AUTHOR]

Photoreceptor composition and retinal visual pigments in three newt ( Caudata, Salamandridae, Pleurodelinae) species ( Pleurodeles waltl, Lissotriton (Triturus) vulgaris, and Cynops orientalis) were studied by light microscopy and single-cell microspectrophotometry. Retinas of all three species contain 'red' (rhodopsin/porphyropsin) rods, large and small single cones, and double cones. Large single cones and both components of double cones contain red-sensitive (presumably LWS) visual pigment whose absorption spectrum peaks between 593 and 611 nm. Small single cones are either blue- (SWS2, maximum absorption between 470 and 489 nm) or UV-sensitive (SWS1, maximum absorption between 340 and 359 nm). Chromophore composition of visual pigments (A vs. A) was assessed both from template fitting of absorption spectra and by the method of selective bleaching. All pigments contained a mixture of A (11- cis retinal) and A (11- cis-3,4-dehydroretinal) chromophore in the proportion depending on the species and cell type. In all cases, A was dominant. However, in C. orientalis rods the fraction of A could reach 45%, while in P. waltl and L. vulgaris cones it did not exceed 5%. Remarkably, the absorption of the newt blue-sensitive visual pigment was shifted by up to 45 nm toward the longer wavelength, as compared with all other amphibian SWS2-pigments. We found no 'green' rods typical of retinas of Anura and some Caudata (ambystomas) in the three newt species studied. [ABSTRACT FROM AUTHOR]

For over the last 2 decades, positively selected amino acid sites have been inferred almost exclusively by showing that the number of nonsynonymous substitutions per nonsynonymous site (dn) is greater than that of synonymous substitutions per synonymous site (ds). However, virtually none of these statistical results have been experimentally tested and remain as hypotheses. To perform such experimental tests, we must connect genotype and phenotype and relate the phenotypic changes to the environmental and behavioral changes of the organism. The genotype–phenotype relationship can be established only by synthesizing and manipulating “proper” ancestral phenotypes, whereas the actual functions of adaptive mutations can be learned by studying their chemical roles in phenotypic changes. [ABSTRACT FROM PUBLISHER]

Abstract: Vertebrate vision in rod photoreceptors begins when a photon hits the visual pigment rhodopsin (Rh) and triggers the phototransduction cascade. Although the fine biochemical and biophysical details of this paradigmatic signalling pathway have been studied for decades, phototransduction still presents unclear mechanistic aspects. Increasing lines of evidence suggest that the visual pigment rhodopsin (Rh) is natively organized in dimers on the surface of disc membranes, and may form higher order “paracrystalline” assemblies, which are not easy to reconcile with the classical collision-coupling mechanistic scenario evoked to explain the extremely fast molecular processes required in phototransduction. The questioned and criticized existence of paracrystalline Rh rafts can be fully accepted only if it can be explained in functional terms by a solid mechanistic picture. Here we discuss how recent data suggest a physiological role for supramolecular assemblies of Rh and its cognate G protein transducin (Gt), which by forming transient complexes in the dark may ensure rapid activation of the cascade even in a crowded environment that, according to the classical picture, would otherwise stop the cascade. [Copyright &y& Elsevier]

Background: The therapeutic effects of Meriva®, a curcumin-phospholipid (lecithin) delivery system (formulated as Norflo® tablets), on visual acuity and retinal thickness in patients with acute and chronic central serous chorioretinopathy was previously investigated in a six-month open-label study. Methods: In this follow-up study, visual acuity was again assessed by ophthalmologic evaluation and retinal thickness by optical coherence tomography (OCT). Norflo tablets were administered twice daily to patients with central serous chorioretinopathy. The study group consisted of 12 patients (total 18 eyes) who completed 12 months of follow-up. The primary endpoint was change in visual acuity before and after treatment with Norflo, and change in neuroretinal or retinal pigment epithelium detachment on OCT was the secondary endpoint. Results: After 12 months of therapy, no eyes showed further reduction in visual acuity, 39% showed stabilization, and 61% showed statistically significant improvement (P = 0.0001 by Student's t-test and P = 0.0005 by Wilcoxon signed rank test). Ninety-five percent of eyes showed a reduction in neuroretinal or retinal pigment epithelium detachment and 5% showed stabilization. The difference in retinal thickness after 12 months was statistically significant (P = 0.0001 by Student's t-test and P = 0.0004 by Wilcoxon signed rank test). Conclusion: These results, albeit preliminary, confirm our previous finding that this curcumin delivery system is effective in the management of central serous chorioretinopathy. When administered in a bioavailable formulation, curcumin is worth considering as a therapeutic agent for the management of inflammatory and degenerative eye conditions involving activation of retinal microglial cells. [ABSTRACT FROM AUTHOR]

How the light-induced transducin (Gt) activation process differs biochemically between cone visual pigments and rod visual pigment (rhodopsin) has remained unclear, because the Gt-activating state (Meta-II) of cone visual pigment decays too fast to precisely measure the activation efficiency by conventional biochemical methods such as the GTPγS binding assay. Here we measured the activation efficiencies of chicken green-sensitive cone visual pigment (cG) and bovine rhodopsin (bRh) in real time by monitoring the intrinsic fluorescence of tryptophan residues in the pigments and Gt. Michaelis-Menten analysis of Gt activation showed that the initial velocity for cG was approximately half that for bRh, while their Michaelis constants were comparable. Gt activation by cG was immediately slowed because of the fast hydrolysis of the retinal Schiff base in Meta-II, but this hydrolysis was suppressed by forming the complex with Gt. Using mutants of cG and bRh for positions 122 and 189, which exhibit altered rates of chromophore hydrolysis in Meta-II, we found that the initial velocity of Gt activation is negatively correlated with the rate of chromophore hydrolysis. These results suggest that the amino acid residues at positions 122 and 189 account for not only the resistance to the chromophore hydrolysis in Meta-II but also the conformation of Meta-II for efficient Gt activation. The substantially longer lifetime of the Gt activating state of Rh would be necessary to suppress the spontaneous quenching by the stochastic decay of the Gt-activating state when a rod responds to a single photon. [ABSTRACT FROM AUTHOR]

The effect of audiovisual interactions on size perception has yet to be examined, despite its fundamental importance in daily life. Previous studies have reported that object length can be estimated solely on the basis of the sounds produced when an object is dropped. Moreover, it has been shown that people typically and easily perceive the correspondence between object sizes and sound intensities. It is therefore possible that auditory stimuli may act as cues for object size, thereby altering the visual perception of size. Thus, in the present study we examined the effects of auditory stimuli on the visual perception of size. Specifically, we investigated the effects of the sound intensity of auditory stimuli, the temporal window of audiovisual interactions, and the effects of the retinal eccentricity of visual stimuli. The results indicated that high-intensity auditory stimuli increased visually perceived object size, and that this effect was especially strong in the peripheral visual field. Additional consideration indicated that this effect on the visual perception of size is induced when the cue reliability is relatively higher for the auditory than for the visual stimuli. In addition, we further suggest that the cue reliabilities of visual and auditory stimuli relate to retinal eccentricity and sound intensity, respectively. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to examine the baseline echographic features in culture-positive and culture-negative endophthalmitis and to correlate these echographic features with final visual outcomes. Methods: We identified a retrospective noncomparative case series of patients with a clinical diagnosis of endophthalmitis and a baseline echographic examination between 1996 and 2010 at a single institution. Graded echographic features studied included: dense, moderate, and mild vitreous opacities; marked, moderate, and mild vitreous membranes; retinal detachment; and choroidal detachment. These were compared between culture-negative, coagulase-negative staphylococci, and other culture-positive cases of endophthalmitis, and were correlated with final visual outcomes. Results: Of 149 patients reviewed, 60 were culture-negative, 26 grew coagulase-negative staphylococci, and 60 grew other culture-positive species. Three had multiple culture isolates. The presence of dense, moderate, and mild vitreous opacities, marked, moderate, and mild vitreous membranes, retinal detachment, and choroidal detachment was not significantly different between the three groups (P = 0.86, P = 0.56, P = 0.34, P = 0.45, respectively). The presence of advanced echographic features of dense vitreous opacities, marked vitreous membranes, retinal detachment, and choroidal detachment was correlated with poorer visual acuity outcomes (P = 0.005, P = 0.0001, P < 0.0001, and P < 0.0001, respectively).Conclusion: No correlation could be made between echographic features and the organism. The presence of advanced echographic features, such as dense vitreous opacities, marked vitreous membranes, retinal detachment, and choroidal detachment, was correlated with worse visual outcomes. [ABSTRACT FROM AUTHOR]

Background: To evaluate the presence and extent of metamorphopsia using M-CHARTSTM (Inami Co., Tokyo, Japan) in patients with central serous chorioretinopathy (CSC). Design: Retrospective consecutive medical record review in a university hospital. Materials and Methods: We examined 33 eyes of 33 consecutive CSC patients using M-CHARTS, which yields scores reflecting the severity of metamorphopsia. The condition was considered present when an M-CHARTS score was 0.3 or over. In all patients, optical coherence tomography (OCT) was performed, best-corrected visual acuity (BCVA) was assessed, and M-CHARTS scores were calculated at the first and the 1- and 3-month follow-up visits. The correlation between M-CHARTS scores and BCVA values was determined. We also sought to define relationships between the level of metamorphopsia and specific OCT findings. Results: Of 33 CSC patients, 15 showed symptoms of metamorphopsia, and all 15 had M-CHARTS scores of over 0.3. However, no correlation was evident between BCVA values and the extent of metamorphopsia as determined using M-CHARTS. In metamorphopsia patients, the incidence of focal retinal pigment epithelial detachment was notably greater than in the non-metamorphopsia group (P = 0.03). Conclusion: M-CHARTS is valuable for monitoring subjective symptom improvement during the clinical course of CSC. M-CHARTS serves as a useful adjunct to OCT. [ABSTRACT FROM AUTHOR]

Purposes: (1) To evaluate the association between expression of α-smooth muscle actin (α-SMA) in proliferative vitreoretinopathy (PVR) and the pathological grading of PVR, and the effect of platelet-derived growth factor (PDGF) on the expression of α-SMA by human retinal pigment epithelial (RPE) cells. (2) To investigate the potential induction of PDGF on the proliferation and migration of human RPE cells as well as the signaling pathways responsible. Methods: We immunohistochemically investigated the expression of α-SMA in PVR. To further investigate the effect of PDGF and the downstream signaling, exogenous PDGF-BB and signaling inhibitors were added to cultured human RPE cells. The MTT method was performed to detected cell proliferation, while cell migration was also measured. Results: α-SMA expression was positively correlated with the pathological grading of PVR. PDGF-BB could stimulate the proliferation and migration of cultured RPE cells through the participation of mitogen-activated protein kinase. In addition, PDGF induced α-SMA expression. The promotion of proliferate/migration and α-SMA expression by PDGF-BB was enhanced by the presence of serum. Conclusions: PDGF and α-SMA are 2 potential therapeutic targets for the treatment of PVR. [ABSTRACT FROM AUTHOR]

The article describes the case of a 28-year-old woman who was examined because of uncomplicated traumatic corneal erosion. It describes the ocular findings before and after the diagnosis of acute exudative polymorphous vitelliform maculopathy. It concluded that the condition may be associated with primarily affected retinal pigment epithelium.