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Photoreceptors (PRs) and retinal pigment epithelial (RPE) cells form a functional unit called the PR-RPE complex. The PR-RPE complex plays a critical role in maintaining retinal homeostasis and function, and the quantification of its structure and topographical arrangement across the macula are important for understanding the etiology, mechanisms, and progression of many retinal diseases. However, the three-dimensional cellular morphology of the PR-RPE complex in living human eyes has not been completely described due to limitations in imaging techniques. We used the cellular resolution and depth-sectioning capabilities of a custom, high-speed Fourier domain mode-locked laser-based adaptive optics-optical coherence tomography (FDML-AO-OCT) platform to characterize human PR-RPE complex topography across the temporal macula from eleven healthy volunteers. With the aid of a deep learning algorithm, key metrics were extracted from the PR-RPE complex of averaged AO-OCT volumes including PR and RPE cell density, PR outer segment length (OSL), and PR/RPE ratio. We found a tight grouping among our cohort for PR density, with a mean (±SD) value of 53,329 (±8106) cells/mm 2 at 1° decreasing to 8669 (±737) cells/mm 2 at 12°. We observed a power function relationship between eccentricity and both PR density and PR/RPE ratio. We found similar variability in our RPE density measures, with a mean value of 7335 (±681) cells/mm 2 at 1° decreasing to 5547 (±356) cells/mm 2 at 12°, exhibiting a linear relationship with a negative slope of -123 cells/mm 2 per degree. OSL monotonically decreased from 33.3 (±2.4) µm at 1° to 18.0 (±1.8) µm at 12°, following a second-order polynomial relationship. PR/RPE ratio decreased from 7.3 (±0.9) µm at 1° to 1.5 (±0.1) µm at 12°. The normative data from this investigation will help lay a foundation for future studies of retinal pathology.

Backgroud: To investigate the safety of repetitive low-level red-light therapy (RLRLT) in children with myopia., Methods: Children with myopia were assigned to the RLRL and control groups. Axial length (AL) and spherical equivalent refraction (SER) were followed up at 3-, 6-, and 12-month. To evaluate the safety of RLRLT, at 6 and 12 months in the RLRL group, multifocal electroretinography (mfERG) and contrast sensitivity were recorded. Furthermore, optical coherence tomography was used to measure the relative reflectance of the ellipsoid zone (rEZR), photoreceptor outer segment (rPOSR), and retinal pigment epithelium (rRPER)., Results: A total of 108 children completed the trial (55 in the RLRL group and 53 in the control group). After 3, 6, and 12 months, AL was shorter and SER less myopic in the RLRL group than in the control group. Regarding the safety of the RLRLT, the response density and amplitude of the P1 wave of the first ring of the mfERG increased significantly at 6 months (P = 0.001 and P = 0.017, respectively). At 6 and 12 months, contrast sensitivity at the high spatial frequency increased. Moreover, the rEZR increased significantly at 6 months (P = 0.029), the rPOSR increased significantly at 6 and 12 months (both P < 0.001), and the increase in rPOSR was greater with greater AL regression., Conclusions: Based on retinal function and structure follow-up, RLRLT was safe within 12 months. However, rEZR and rPOSR increased, the effects of this phenomenon requires further observation., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024. Published by Elsevier B.V.)

The functionality of photoreceptors, rods, and cones is highly dependent on their outer segments (POS), a cellular compartment containing highly organized membranous structures that generate biochemical signals from incident light. While POS formation and degeneration are qualitatively assessed on microscopy images, reliable methodology for quantitative analyses is still limited. Here, we developed methods to quantify POS (QuaPOS) maturation and quality on retinal sections using automated image analyses. POS formation was examined during the development and in adulthood of wild-type mice via light microscopy (LM) and transmission electron microscopy (TEM). To quantify the number, size, shape, and fluorescence intensity of POS, retinal cryosections were immunostained for the cone POS marker S-opsin. Fluorescence images were used to train the robust classifier QuaPOS-LM based on supervised machine learning for automated image segmentation. Characteristic features of segmentation results were extracted to quantify the maturation of cone POS. Subsequently, this quantification method was applied to characterize POS degeneration in "cone photoreceptor function loss 1" mice. TEM images were used to establish the ultrastructural quantification method QuaPOS-TEM for the alignment of POS membranes. Images were analyzed using a custom-written MATLAB code to extract the orientation of membranes from the image gradient and their alignment (coherency). This analysis was used to quantify the POS morphology of wild-type and two inherited retinal degeneration ("retinal degeneration 19" and "rhodopsin knock-out") mouse lines. Both automated analysis technologies provided robust characterization and quantification of POS based on LM or TEM images. Automated image segmentation by the classifier QuaPOS-LM and analysis of the orientation of membrane stacks by QuaPOS-TEM using fluorescent or TEM images allowed quantitative evaluation of POS formation and quality. The assessments showed an increase in POS number, volume, and membrane coherency during wild-type postnatal development, while a decrease in all three observables was detected in different retinal degeneration mouse models. All the code used for the presented analysis is open source, including example datasets to reproduce the findings. Hence, the QuaPOS quantification methods are useful for in-depth characterization of POS on retinal sections in developmental studies, for disease modeling, or after therapeutic interventions affecting photoreceptors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Seidemann, Salomon, Hoffmann, Kurth, Sbalzarini, Haase and Ader.)

Background: The photoreceptor outer segment (PROS) layer demonstrates focal thinning above the fluorescein leakage in acute central serous chorioretinopathy (CSC); however, the nature of this phenomenon is not known., Objectives: To study the relationship between the PROS layer and thickness of the outer retinal layers above the fluorescein leakage in newly diagnosed acute CSC., Design: Single-center retrospective study., Methods: All participants received multimodal imaging, including fluorescein angiography and optical coherence tomography. Thickness of PROS, outer nuclear layer (ONL), and ONL-outer plexiform layer (OPL) complex was measured above the leakage and outside the leakage within the area of neurosensory detachment. The number of intraretinal hyperreflective foci of the outer retina was counted. The correlation between PROS thickness and ONL, OPL-ONL complex thickness, and the number of intraretinal hyperreflective foci was calculated., Results: Fifty eyes of 48 patients (38 males and 10 females, 43.8 ± 10.6 years) with a mean symptom duration of 1.4 ± 1.3 months were included. PROS thickness above the fluorescein leakage showed a statistically significant correlation with ONL thickness, OPL-ONL complex thickness, and the number of hyperreflective foci in the outer retina, 0.57, 0.60, and -0.46, respectively ( p  < 0.001). Measuring the extent of PROS thinning above the leakage in newly diagnosed CSC allowed to predict self-resolution of subretinal fluid. The greatest linear dimension of PROS thinning showed an area under the receiver operating curve (ROC) curve of 0.98. The cases without PROS thinning had the fastest resolution of subretinal fluid., Conclusion: PROS thinning above the fluorescein leakage in acute CSC is associated with thinning of the outer retinal layers and reveals mild outer retinal atrophy. The absence of PROS thinning predicts faster resolution of CSC., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2023.)

Retinal pigment epithelium (RPE) cells daily ingest the tips of the photoreceptor outer segments (POSs), with phagosome number varying throughout a 24-h cycle. A major focus in the literature has been on a peak in phagosome concentration shortly after lights-on. Moreover, this peak has frequently been inferred to represent a peak in POS tip ingestion. Here, we have reviewed old and new literature on the daily cycle of phagosome number in the RPE and conclude that there is more variation in the timing of phagosome concentration peaks than is currently acknowledged. We also discuss that phagosome quantity is affected by the rate of phagosome degradation as well as the rate of ingestion; given that phagosome half-life may not be constant throughout the daily cycle, maximal POS ingestion may not necessarily coincide with a peak in phagosome concentration., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Four clinical cases of patients with rhegmatogenous retinal detachment (RRD) associated with elevated intraocular pressure (IOP) are described. All the patients were men who came to the emergency service with floaters, all presented mild to moderate inflammation in the anterior chamber and increased intraocular pressure greater than 30 mmHg. All were diagnosed of RRD. This demonstrates that a RRD does not always present low IOP. In these cases of clinical retinal pathology and high IOP, we must carefully examine the anterior chamber and the fundus of the eye so that an associated retinal detachment does not remain unnoticed, and can be treated immediately. This association of elevated IOP and RRD is called as Schwartz-Matsuo Syndrome. 1 ., (Copyright © 2022 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.)

Purpose: To describe optical coherence tomography (OCT) characteristics of central serous chorioretinopathy (CSCR) without any hyperfluorescent leakage on fundus fluorescein angiography (FFA)., Methods: This was a multicentric, retrospective, observational study of ten eyes of ten patients with CSCR without any hyperfluorescence leakage on FFA. Baseline patient characteristics, best corrected visual acuity, and OCT parameters like relative retinal pigment epithelium (RPE) reflectivity at the presumed leak site and control site were measured., Results: Increased macular thickness, neurosensory detachment, and choroidal thickness were seen at the site of maximum subretinal fluid (SRF). Out of ten eyes, nine had photoreceptor outer segment (PROS) disruption (46% ± 26.33%) at the site of SRF pocket, and five had presumed former leak site characterized by PROS thinning. The presumed leak site demonstrated higher RPE reflectivity compared to the control site (0.92 ± 0.04 vs. 0.87 ± 0.04; P = 0.0058)., Conclusion: CSCR without hyperfluorescent leakage on FFA may have PROS damage and changes in RPE hyperreflectivity., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Current Ophthalmology.)

Retinal photoreceptors undergo daily renewal of their distal outer segments, a process indispensable for maintaining retinal health. Photoreceptor outer segment (POS) phagocytosis occurs as a daily peak, roughly about 1 hour after light onset. However, the underlying cellular and molecular mechanisms which initiate this process are still unknown. Here we show that, under constant darkness, mice deficient for core circadian clock genes (Per1 and Per2) lack a daily peak in POS phagocytosis. By qPCR analysis, we found that core clock genes were rhythmic over 24 hours in both WT and Per1, Per2 double mutant whole retinas. More precise transcriptomics analysis of laser capture microdissected WT photoreceptors revealed no differentially expressed genes between time points preceding and during the peak of POS phagocytosis. In contrast, we found that microdissected WT retinal pigment epithelium (RPE) had a number of genes that were differentially expressed at the peak phagocytic time point compared to adjacent ones. We also found a number of differentially expressed genes in Per1, Per2 double mutant RPE compared to WT ones at the peak phagocytic time point. Finally, based on STRING analysis, we found a group of interacting genes that potentially drive POS phagocytosis in the RPE. This potential pathway consists of genes such as: Pacsin1, Syp, Camk2b, and Camk2d among others. Our findings indicate that Per1 and Per2 are necessary clock components for driving POS phagocytosis and suggest that this process is transcriptionally driven by the RPE., (© 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Background: Biomarkers are characteristic biological measurable signs and objective parameters to detect the state of health. Besides functional and temporal factors, imaging biomarkers play an increasingly important role. In full-thickness and lamellar defects of the macula numerous imaging parameters have been described. This knowledge resulted in new classifications for both clinical pictures, which are based on important biomarkers of these clinical pictures and characteristic features of described subtypes., Methods: Imaging biomarkers for full-thickness and lamellar macular defects are described with respect to the classification and their functional prognostic importance. The importance of these biomarkers is presented., Results: The current classification of full-thickness and lamellar macular defects is based on structural biomarkers. Biomarkers are important for prognostic and therapeutic evaluation and they have an impact on the surgical strategy. There are various surgical strategies for treatment of full-thickness macular holes depending on the size of the foramen and other biomarkers. The inverted ILM flap technique improves the closure rate of large macular holes. In lamellar macular holes showing signs of progression an early surgical intervention results in a good anatomical and functional prognosis., Conclusion: Multimodal diagnostics provide important preoperative, intraoperative, and postoperative features for macular holes and lamellar macular holes, which are essential biomarkers for the exact classification, the therapeutic strategy and for assessment of the prognosis.

Photoreceptor disease results in irreparable vision loss and blindness, which has a dramatic impact on quality of life. Pathogenic mutations in RP1L1 lead to photoreceptor degenerations such as occult macular dystrophy and retinitis pigmentosa. RP1L1 is a component of the photoreceptor axoneme, the backbone structure of the photoreceptor's light-sensing outer segment. We generated an rp1l1 zebrafish mutant using CRISPR/Cas9 genome editing. Mutant animals had progressive photoreceptor functional defects as determined by electrophysiological assessment. Optical coherence tomography showed gaps in the photoreceptor layer, disrupted photoreceptor mosaics, and thinner retinas. Mutant retinas had disorganized photoreceptor outer segments and lipid-rich subretinal drusenoid deposits between the photoreceptors and retinal pigment epithelium. Our mutant is a novel model of RP1L1 -associated photoreceptor disease and the first zebrafish model of photoreceptor degeneration with reported subretinal drusenoid deposits, a feature of age-related macular degeneration.

Purpose: To quantitatively investigate the reflectivity and structure of the outer retinal layers on spectral-domain optical coherence tomography (SD-OCT) in commotio retinae., Methods: Nineteen patients with acute macular commotio retinae and 19 age-matched normal controls were examined using SD-OCT. Longitudinal reflectance profiles (LRP) were obtained using Image J. The reflectivity of outer retinal layers was measured at the fovea, 1 mm nasal to fovea and 1 mm temporal to fovea. The reflectivity ratios of outer retinal layers divided by the outer nuclear layer (ONL) were calculated for normalization. Photoreceptor outer segment layer thickness was also measured. The results were compared between the patients and controls., Results: The reflectivity ratio of ellipsoid zone/ONL and outer segment/ONL was higher in commotio retinae than in controls only at fovea (12.66 ± 4.73 vs 9.67 ± 3.34, p = 0.041; 7.70 ± 2.20 vs 3.73 ± 1.63, p < 0.001, respectively) but not at 1 mm nasal or temporal to the fovea. Photoreceptor outer segment layer thickness was significantly shorter in commotio retinae compared to controls at all three locations (19.64 ± 3.05 vs 25.16 ± 3.53, 16.95 ± 4.02 vs 20.00 ± 3.00, and 15.42 ± 3.22 vs 20.05 ± 2.48, respectively, all p < 0.05)., Conclusions: Quantitative measurement of SD-OCT images revealed that shortening of photoreceptor outer segment is an additional, and potentially better, biomarker for commotio retinae on top of increased reflectivity.

Rod and cone photoreceptor outer segment (OS) structural integrity is essential for normal vision; disruptions contribute to a broad variety of retinal ciliopathies. OSs possess many hundreds of stacked membranous disks, which capture photons and scaffold the phototransduction cascade. Although the molecular basis of OS structure remains unresolved, recent studies suggest that the photoreceptor-specific tetraspanin, peripherin-2/rds (P/rds), may contribute to the highly curved rim domains at disk edges. Here, we demonstrate that tetrameric P/rds self-assembly is required for generating high-curvature membranes in cellulo, implicating the noncovalent tetramer as a minimal unit of function. P/rds activity was promoted by disulfide-mediated tetramer polymerization, which transformed localized regions of curvature into high-curvature tubules of extended lengths. Transmission electron microscopy visualization of P/rds purified from OS membranes revealed disulfide-linked tetramer chains up to 100 nm long, suggesting that chains maintain membrane curvature continuity over extended distances. We tested this idea in Xenopus laevis photoreceptors, and found that transgenic expression of nonchain-forming P/rds generated abundant high-curvature OS membranes, which were improperly but specifically organized as ectopic incisures and disk rims. These striking phenotypes demonstrate the importance of P/rds tetramer chain formation for the continuity of rim formation during disk morphogenesis. Overall, this study advances understanding of the normal structure and function of P/rds for OS architecture and biogenesis, and clarifies how pathogenic loss-of-function mutations in P/rds cause photoreceptor structural defects to trigger progressive retinal degenerations. It also introduces the possibility that other tetraspanins may generate or sense membrane curvature in support of diverse biological functions., Competing Interests: The authors declare no competing interest.

Background: In large full thickness macular holes (FTMH) the closure rate after vitrectomy and conventional internal limiting membrane (ILM) peeling is less than 90%. The aim of this study was to examine the visual acuity and anatomical success rate with high-resolution optical coherence tomography (OCT) after transconjunctival sutureless 23-gauge pars plana vitrectomy as well as intraoperative OCT (iOCT) and Brilliant Peel (BP)-assisted ILM peeling using the inverted ILM flap technique in patients with large FTMHs., Method: In this retrospective study 25 eyes of 25 consecutive patients with large FTMH were treated by 23-G vitrectomy with BP and iOCT-assisted ILM peeling using the inverted ILM flap technique followed by gas tamponade. In all patients best corrected visual acuity (BCVA) and the maximum diameter, base and height of the FTMH as well as intraretinal alterations were measured preoperatively using high-resolution spectral domain OCT (SD-OCT, Spectralis, Heidelberg Engineering, Germany). The BCVA was measured after 1, 3, and 6 months. Additionally, the closure rate and the microstructural integrity of the outer retinal layers, e.g. external limiting membrane (ELM), ellipsoid zone und photoreceptor outer segment (OS) were registered in the SD-OCT and correlated with the results of BCVA after macular hole surgery., Results: In all surgical procedures with the inverted ILM flap technique the application of iOCT enabled a good visualization and a controlled positioning of the ILM flaps. At baseline mean BCVA was 0.2 (0.7 logMAR) and improved significantly after 1, 3 und 6 months to 0.4 (0.4 logMAR), 0.5 (0.3 logMAR) and 0.63 (0.2 logMAR), respectively. The closure rate of the FTMHs was 100%. Microstructural integrity of the outer retinal layers was evaluated semiquantitatively and showed good correlation with BCVA., Conclusion: Vitrectomy with BP and iOCT-assisted ILM peeling using the inverted ILM flap technique in patients with large FTMH is a very controlled and safe microsurgical strategy and shows good functional and anatomical results. The morphology of the FTMH, the ILM flap and the position of the inverted ILM flap under air was well visualized by IOCT. The microstructural integrity of the outer retinal layers is displayed in detail on SD-OCT and represents an important predictive parameter for BCVA after macular hole surgery.

Arf-like protein 13b (ARL13b) is a small GTPase that functions as a guanosine nucleotide exchange factor (GEF) for ARL3-GDP. ARL13b is located exclusively in photoreceptor outer segments (OS) presumably anchored to discs by palmitoylation, whereas ARL3 is an inner segment cytoplasmic protein. Hypomorphic mutations affecting the ARL13b G-domain inactivate GEF activity and lead to Joubert syndrome (JS) in humans. However, the molecular mechanisms in ARL13b mutation-induced Joubert syndrome, particularly the function of primary cilia, are still incompletely understood. Because Arl13b germline knockouts in mouse are lethal, we generated retina-specific deletions of ARL13b in which ARL3-GTP formation is impaired. In mouse ret Arl13b -/- central retina at postnatal day 6 (P6) and older, outer segments were absent, thereby preventing trafficking of outer segment proteins to their destination. Ultrastructure of postnatal day 10 (P10) central ret Arl13b -/- photoreceptors revealed docking of basal bodies to cell membranes, but mature transition zones and disc structures were absent. Deletion of ARL13b in adult mice via tamoxifen-induced Cre/loxP recombination indicated that axonemes gradually shorten and outer segments progressively degenerate. IFT88, essential for anterograde intraflagellar transport (IFT), was significantly reduced at tam Arl13b -/- basal bodies, suggesting impairment of intraflagellar transport. AAV2/8 vector-mediated ARL13b expression in the ret Arl13b -/- retina rescued ciliogenesis., (© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.)

Retinal pigment epithelium (RPE) cells take part in retinal preservation, such as phagocytizing the shed photoreceptor outer segments (POS), every day. The incomplete phagocytic function accelerates RPE degeneration and formation of the toxic by-product lipofuscin. Excessive lipofuscin accumulation is characteristic of various blinding diseases in the human eye. Progranulin is a cysteine-rich protein that has multiple biological activities, and it has a high presence in the retina. Progranulin has been recognized to be involved in macrophage phagocytosis in the brain. The purpose of this study is to determine whether progranulin influences phagocytosis by RPE cells. All experiments were performed on primary human RPE (hRPE) cells in culture. pHrodo was used to label the isolated porcine POS, and quantification of pHrodo fluorescence was used to determine the degree of phagocytosis. Western blotting and immunohistochemistry of key proteins involved in phagocytosis were used to clarify the mechanism of progranulin. Progranulin increased RPE phagocytosis in hydrogen peroxide-treated and nontreated RPE cells. The phosphorylated form of Mer tyrosine kinase, which is important for POS internalization, was significantly increased in the progranulin-exposed cells. This increase was attenuated by SU11274, an inhibitor of hepatic growth factor receptor. Under the oxidative stress condition, exposure to progranulin led to an approximately twofold increase in integrin alpha-v, which is associated with the first step in recognition of POS by RPE cells. These results suggest that progranulin could be an effective stimulator for RPE phagocytosis and could repair RPE function. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

The retinal pigment epithelium (RPE) is a post-mitotic epithelial monolayer situated between the light-sensitive photoreceptors and the choriocapillaris. Given its vital functions for healthy vision, the RPE is a primary target for insults that result in blinding diseases, including age-related macular degeneration (AMD). One such function is the phagocytosis and digestion of shed photoreceptor outer segments. In the present study, we examined the process of trafficking of outer segment disk membranes in live cultures of primary mouse RPE, using high speed spinning disk confocal microscopy. This approach has enabled us to track phagosomes, and determine parameters of their motility, which are important for their efficient degradation.

Purpose: To investigate near-infrared reflectance (NIR) findings in central serous chorioretinopathy (CSCR) and to predict the choroidal vascular diffuse hyperpermeability (CVDHP) by NIR and enhanced depth imaging spectral-domain optical coherence tomography (EDI SD-OCT) noninvasively., Methods: Retrospective analysis of 52 eyes of 50 CSCR patients with serous macular detachment. All patients received NIR, indocyanine green angiography (ICGA), and EDI SD-OCT. NIR patterns (irregular, defected, masked and enhanced), double layer sign (DLS) in EDI SD-OCT and CVDHP in ICGA were evaluated. In addition, we measured the length of photoreceptor outer segment (LPOS), and subfoveal choroidal thickness (SFCT) by Heidelberg eye explorer software. Moreover, the integrity of the junction of inner segment and outer segment of photoreceptor (IS/OS) was recorded., Results: 42 (80.8%) eyes were identified with CVDHP, and 10 (19.2%) eyes appeared disrupted IS/OS. Irregular NIR pattern was found in 48 (92.3%) eyes, as well as DLS was observed in 37 (71.2%) eyes. In addition, irregular NIR pattern, together with DLS had a significant positive correlation with the occurrence of CVDHP (r=0.605, p<0.0001). Moreover, in IS/OS preserved eyes, there was also a significant positive relationship between CVDHP and LPOS (r=0.599, p<0.0001). In contrast, SFCT only demonstrated a moderate positive relationship with CVDHP in this group (r=0.441, p=0.013<0.05)., Conclusions: Irregular NIR pattern, DLS and LPOS are qualitative and quantitative indexes for CVDHP. Our study suggests that NIR can detect CVDHP effectively and noninvasively. The combined detection of NIR and EDI SD-OCT is a predictive approach for CSCR patients, as a supplement of ICGA., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Purpose: Autosomal dominant Stargardt macular dystrophy caused by mutations in the Elongation of Very Long Chain fatty acids (ELOVL4) gene results in macular degeneration, leading to early childhood blindness. Transgenic mice and pigs expressing mutant ELOVL4 develop progressive photoreceptor degeneration. The mechanism by which these mutations cause macular degeneration remains unclear, but have been hypothesized to involve the loss of an ER-retention dilysine motif located in the extreme C-terminus. Dominant negative mechanisms and reduction in retinal polyunsaturated fatty acids also have been suggested. To understand the molecular mechanisms involved in disease progression in vivo, we addressed the hypothesis that the disease-linked C-terminal truncation mutant of ELOVL4 exerts a dominant negative effect on wild-type (WT) ELOVL4, altering its subcellular localization and function, which subsequently induces retinal degeneration and loss of vision., Methods: We generated transgenic Xenopus laevis that overexpress HA-tagged murine ELOVL4 variants in rod photoreceptors., Results: Tagged or untagged WT ELOVL4 localized primarily to inner segments. However, the mutant protein lacking the dilysine motif was mislocalized to post-Golgi compartments and outer segment disks. Coexpression of mutant and WT ELOVL4 in rods did not result in mislocalization of the WT protein to outer segments or in the formation of aggregates. Full-length HA-tagged ELOVL4 lacking the dilysine motif (K308R/K310R) necessary for targeting the WT ELOVL4 protein to the endoplasmic reticulum was similarly mislocalized to outer segments., Conclusions: We propose that expression and outer segment mislocalization of the disease-linked 5-base-pair deletion mutant ELOVL4 protein alters photoreceptor structure and function, which subsequently results in retinal degeneration, and suggest three possible mechanisms by which mutant ELOVL4 may induce retinal degeneration in STGD3., (Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.)

Neuropeptide Y (NPY) and NPY receptors are widely expressed in the central nervous system, including the retina. Retinal cells, in particular neurons, astrocytes, and Müller, microglial and endothelial cells express this peptide and its receptors (Y1, Y2, Y4 and/or Y5). Several studies have shown that NPY is expressed in the retina of various mammalian and non-mammalian species. However, studies analyzing the distribution of NPY receptors in the retina are still scarce. Although the physiological roles of NPY in the retina have not been completely elucidated, its early expression strongly suggests that NPY may be involved in the development of retinal circuitry. NPY inhibits the increase in [Ca(2+)]i triggered by elevated KCl in retinal neurons, protects retinal neural cells against toxic insults and induces the proliferation of retinal progenitor cells. In this review, we will focus on the roles of NPY in the retina, specifically proliferation, neuromodulation and neuroprotection. Alterations in the NPY system in the retina might contribute to the pathogenesis of retinal degenerative diseases, such as diabetic retinopathy and glaucoma, and NPY and its receptors might be viewed as potentially novel therapeutic targets., (Copyright © 2013 Elsevier Ltd. All rights reserved.)