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The Journal of Biological Chemistry Jan 2012Activation of the visual pigment by light in rod and cone photoreceptors initiates our visual perception. As a result, the signaling properties of visual pigments,... (Review)
Review
Activation of the visual pigment by light in rod and cone photoreceptors initiates our visual perception. As a result, the signaling properties of visual pigments, consisting of a protein, opsin, and a chromophore, 11-cis-retinal, play a key role in shaping the light responses of photoreceptors. The combination of pharmacological, physiological, and genetic tools has been a powerful approach advancing our understanding of the interactions between opsin and chromophore and how they affect the function of visual pigments. The signaling properties of the visual pigments modulate many aspects of the function of rods and cones, producing their unique physiological properties.
Topics: Animals; Humans; Opsins; Retinal Cone Photoreceptor Cells; Retinal Rod Photoreceptor Cells; Retinaldehyde; Signal Transduction; Vision, Ocular
PubMed: 22074928
DOI: 10.1074/jbc.R111.303008 -
Ophthalmic Research 2019Autophagy is a lysosomal degradation process that maintains cellular homeostasis by removing dysfunctional organelles and unfolded proteins. Increasing evidence has... (Review)
Review
Autophagy is a lysosomal degradation process that maintains cellular homeostasis by removing dysfunctional organelles and unfolded proteins. Increasing evidence has shown that autophagy proteins are involved in retinal physiology and pathology and that defective autophagy contributes to retinal degeneration. In retinal diseases, autophagy plays a dual role: promoting retinal cell survival and death. Autophagy at a normal level helps retinal cells defend themselves against harmful stress; however, excessive autophagy results in retinal deterioration. Both synergistic and antagonistic roles of autophagy and apoptosis in the retina have been reported in the literature. In this review, we summarize the roles of autophagy in the development of the retina and retinal diseases. This review highlights the importance of autophagy in retinal diseases, and targeting autophagy may provide a new therapeutic approach for retinal diseases.
Topics: Animals; Apoptosis; Autophagy; Cell Survival; Humans; Inflammation; Retina; Retinitis
PubMed: 29694961
DOI: 10.1159/000487486 -
Scientific Reports Dec 2020To evaluate extralesional microvascular and structural changes of the macula using optical coherence tomography angiography (OCTA) and structural OCT in cytomegalovirus... (Observational Study)
Observational Study
To evaluate extralesional microvascular and structural changes of the macula using optical coherence tomography angiography (OCTA) and structural OCT in cytomegalovirus retinitis (CMVR). An observational study of CMVR patients were performed. Complete ophthalmic examination, serial color fundus photography, structural OCT and OCTA were performed at baseline and follow-up visits for up to 12 months. The structural OCT was analyzed to evaluate macular areas within, bordering and beyond the CMVR lesions. Extralesional retinal capillary plexus of the macula were evaluated by OCT angiography and compared with the unaffected fellow eyes. Thirteen eyes from 13 patients were enrolled. At baseline, macular areas without CMVR lesions showed decreased vessel density (VD) of both the superficial (P = 0.0002) and deep (P < 0.0001) retinal capillary plexus in eyes with CMVR as compared with the corresponding macular areas of the unaffected fellow eyes. The decrease of VD persisted through the follow-up period for up to 12 months after adjusting for degree of vitreous haze. Structural macular OCT characteristics at the borders and beyond the lesions included intraretinal hyperreflective dots, cystoid macular edema, subretinal fluid and selective ellipsoid zone (EZ) loss. The selective EZ loss found in 6 of 12 eyes showed recovery in 4 eyes after receiving anti-viral treatment. In CMVR eyes, there were microvascular and microstructural abnormalities in the macular area without clinically visible CMVR lesions. Our results provided interesting insights into CMV infection of the retina.
Topics: Adult; Cytomegalovirus Retinitis; Female; Fluorescein Angiography; Humans; Macula Lutea; Male; Microvascular Density; Middle Aged; Tomography, Optical Coherence; Young Adult
PubMed: 33293646
DOI: 10.1038/s41598-020-78587-6 -
Philosophical Transactions of the Royal... Oct 2009Recent findings shed light on the steps underlying the evolution of vertebrate photoreceptors and retina. Vertebrate ciliary photoreceptors are not as wholly distinct... (Review)
Review
Recent findings shed light on the steps underlying the evolution of vertebrate photoreceptors and retina. Vertebrate ciliary photoreceptors are not as wholly distinct from invertebrate rhabdomeric photoreceptors as is sometimes thought. Recent information on the phylogenies of ciliary and rhabdomeric opsins has helped in constructing the likely routes followed during evolution. Clues to the factors that led the early vertebrate retina to become invaginated can be obtained by combining recent knowledge about the origin of the pathway for dark re-isomerization of retinoids with knowledge of the inability of ciliary opsins to undergo photoreversal, along with consideration of the constraints imposed under the very low light levels in the deep ocean. Investigation of the origin of cell classes in the vertebrate retina provides support for the notion that cones, rods and bipolar cells all originated from a primordial ciliary photoreceptor, whereas ganglion cells, amacrine cells and horizontal cells all originated from rhabdomeric photoreceptors. Knowledge of the molecular differences between cones and rods, together with knowledge of the scotopic signalling pathway, provides an understanding of the evolution of rods and of the rods' retinal circuitry. Accordingly, it has been possible to propose a plausible scenario for the sequence of evolutionary steps that led to the emergence of vertebrate photoreceptors and retina.
Topics: Animals; Ciliophora; Evolution, Molecular; Light Signal Transduction; Opsins; Photoreceptor Cells; Photoreceptor Cells, Vertebrate; Retinaldehyde
PubMed: 19720653
DOI: 10.1098/rstb.2009.0102 -
Journal of Investigative Medicine High... 2023Neuroretinitis, originally described by Leber at the turn of the 20th century, has long perplexed ophthalmologists due to its multiple recognized causes and often...
Neuroretinitis, originally described by Leber at the turn of the 20th century, has long perplexed ophthalmologists due to its multiple recognized causes and often atypical presentation. Optic disk edema and macular star in the affected eye are well-agreed upon findings and are due to increased permeability of blood vessels near the optic disk and in the retina at large. It also is universally painless and presents with a relative afferent pupillary defect (RAPD) in the affected eye or eyes. However, depending on the infectious agent, an underlying autoimmune condition, or undefined idiopathic cause, there can be various degrees of vision loss, visual field loss, progression or recurrence, as well as involvement of the other eye. We present this case of presumed sequential idiopathic neuroretinitis with severe vision and visual field loss with a low-positive anti-MOG test in the border county of El Paso.
Topics: Humans; Retinitis; Optic Disk; Chorioretinitis; Diagnosis, Differential
PubMed: 37942586
DOI: 10.1177/23247096231206619 -
Developmental Biology Aug 2021Vitamin A deficiency can cause human pathologies that range from blindness to embryonic malformations. This diversity is due to the lack of two major vitamin A... (Review)
Review
Vitamin A deficiency can cause human pathologies that range from blindness to embryonic malformations. This diversity is due to the lack of two major vitamin A metabolites with very different functions: the chromophore 11-cis-retinal (vitamin A aldehyde) is a critical component of the visual pigment that mediates phototransduction, while the signaling molecule all-trans-retinoic acid regulates the development of various tissues and is required for the function of the immune system. Since animals cannot synthesize vitamin A de novo, they must obtain it either as preformed vitamin A from animal products or as carotenoid precursors from plant sources. Due to its essential role in the visual system, acute vitamin A deprivation impairs photoreceptor function and causes night blindness (poor vision under dim light conditions), while chronic deprivation results in retinal dystrophies and photoreceptor cell death. Chronic vitamin A deficiency is the leading cause of preventable childhood blindness according to the World Health Organization. Due to the requirement of vitamin A for retinoic acid signaling in development and in the immune system, vitamin A deficiency also causes increased mortality in children and pregnant women in developing countries. Drosophila melanogaster is an excellent model to study the effects of vitamin A deprivation on the eye because vitamin A is not essential for Drosophila development and chronic deficiency does not cause lethality. Moreover, genetic screens in Drosophila have identified evolutionarily conserved factors that mediate the production of vitamin A and its cellular uptake. Here, we review our current knowledge about the role of vitamin A in the visual system of mammals and Drosophila melanogaster. We compare the molecular mechanisms that mediate the uptake of dietary vitamin A precursors and the metabolism of vitamin A, as well as the consequences of vitamin A deficiency for the structure and function of the eye.
Topics: Animals; Drosophila melanogaster; Mammals; Photoreceptor Cells; Retina; Retinal Pigment Epithelium; Retinaldehyde; Tretinoin; Vision, Ocular; Visual Perception; Vitamin A; Vitamin A Deficiency
PubMed: 33774009
DOI: 10.1016/j.ydbio.2021.03.013 -
Cell Reports Aug 2023In daylight, demand for visual chromophore (11-cis-retinal) exceeds supply by the classical visual cycle. This shortfall is compensated, in part, by the retinal...
In daylight, demand for visual chromophore (11-cis-retinal) exceeds supply by the classical visual cycle. This shortfall is compensated, in part, by the retinal G-protein-coupled receptor (RGR) photoisomerase, which is expressed in both the retinal pigment epithelium (RPE) and in Müller cells. The relative contributions of these two cellular pools of RGR to the maintenance of photoreceptor light responses are not known. Here, we use a cell-specific gene reactivation approach to elucidate the kinetics of RGR-mediated recovery of photoreceptor responses following light exposure. Electroretinographic measurements in mice with RGR expression limited to either cell type reveal that the RPE and a specialized subset of Müller glia contribute both to scotopic and photopic function. We demonstrate that 11-cis-retinal formed through photoisomerization is rapidly hydrolyzed, consistent with its role in a rapid visual pigment regeneration process. Our study shows that RGR provides a pan-retinal sink for all-trans-retinal released under sustained light conditions and supports rapid chromophore regeneration through the photic visual cycle.
Topics: Animals; Mice; Retinal Pigment Epithelium; Retinaldehyde; Retinal Pigments; Receptors, G-Protein-Coupled; Neuroglia; Retinal Cone Photoreceptor Cells
PubMed: 37585292
DOI: 10.1016/j.celrep.2023.112982 -
Chemical Reviews Jan 2014
Review
Topics: Acyltransferases; Animals; Coenzyme A-Transferases; Humans; Mevalonic Acid; Photoreceptor Cells; Retinal Diseases; Retinaldehyde; Retinoids; Retinol-Binding Proteins; Rhodopsin; cis-trans-Isomerases
PubMed: 23905688
DOI: 10.1021/cr400107q -
International Journal of Molecular... Apr 2021Diabetic retinopathy is characterized by dysfunction of the retinal vascular network, combined with a persistent low-grade inflammation that leads to vision-threatening...
Diabetic retinopathy is characterized by dysfunction of the retinal vascular network, combined with a persistent low-grade inflammation that leads to vision-threatening complications. Netrin-4 (NTN4) is a laminin-related secreted protein and guidance cue molecule present in the vascular basal membrane and highly expressed in the retina. A number of studies inferred that the angiogenic abilities of NTN4 could contribute to stabilize vascular networks and modulate inflammation. Analyzing human specimens, we show that and netrin receptors are upregulated in the diabetic retina. We further evaluated a knock-out model for NTN4 undergoing experimental diabetes induced by streptozotocin. We investigated retina function and immune cells in vivo and demonstrated that NTN4 provides a protective milieu against inflammation in the diabetic retina and prevents cytokine production.
Topics: Animals; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Electroretinography; Gene Expression Regulation; Humans; Mice, Transgenic; Netrins; Retina; Retinitis
PubMed: 33923095
DOI: 10.3390/ijms22094481 -
Proceedings of the National Academy of... Aug 2020The visual phototransduction cascade begins with a - photoisomerization of a retinylidene chromophore associated with the visual pigments of rod and cone photoreceptors.... (Review)
Review
The visual phototransduction cascade begins with a - photoisomerization of a retinylidene chromophore associated with the visual pigments of rod and cone photoreceptors. Visual opsins release their all--retinal chromophore following photoactivation, which necessitates the existence of pathways that produce 11--retinal for continued formation of visual pigments and sustained vision. Proteins in the retinal pigment epithelium (RPE), a cell layer adjacent to the photoreceptor outer segments, form the well-established "dark" regeneration pathway known as the classical visual cycle. This pathway is sufficient to maintain continuous rod function and support cone photoreceptors as well although its throughput has to be augmented by additional mechanism(s) to maintain pigment levels in the face of high rates of photon capture. Recent studies indicate that the classical visual cycle works together with light-dependent processes in both the RPE and neural retina to ensure adequate 11--retinal production under natural illuminances that can span ten orders of magnitude. Further elucidation of the interplay between these complementary systems is fundamental to understanding how cone-mediated vision is sustained in vivo. Here, we describe recent advances in understanding how 11--retinal is synthesized via light-dependent mechanisms.
Topics: Animals; Humans; Light; Light Signal Transduction; Opsins; Retinal Cone Photoreceptor Cells; Retinal Pigment Epithelium; Retinaldehyde; Vision, Ocular
PubMed: 32759209
DOI: 10.1073/pnas.2008211117