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The Biochemical Journal Oct 2018The vitamin A derivative 11-retinaldehyde plays a pivotal role in vertebrate vision by serving as the chromophore of rod and cone visual pigments. In the initial step of... (Review)
Review
The vitamin A derivative 11-retinaldehyde plays a pivotal role in vertebrate vision by serving as the chromophore of rod and cone visual pigments. In the initial step of vision, a photon is absorbed by this chromophore resulting in its isomerization to an all- state and consequent activation of the visual pigment and phototransduction cascade. Spent chromophore is released from the pigments through hydrolysis. Subsequent photon detection requires the delivery of regenerated 11-retinaldehyde to the visual pigment. This conversion is achieved through a process known as the visual cycle. In this review, we will discuss the enzymes, binding proteins and transporters that enable the visual pigment renewal process with a focus on advances made during the past decade in our understanding of their structural biology.
Topics: Amino Acid Sequence; Animals; Crystallography, X-Ray; Humans; Protein Structure, Secondary; Retinal Pigment Epithelium; Retinal Pigments; Retinaldehyde; Vision, Ocular
PubMed: 30352831
DOI: 10.1042/BCJ20180193 -
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 -
Molecular Vision 2022The development of biomaterials provides potent promise for the regeneration of neuroretinal cells in degenerative eye diseases and retinal tissue engineering....
PURPOSE
The development of biomaterials provides potent promise for the regeneration of neuroretinal cells in degenerative eye diseases and retinal tissue engineering. Biomimetic three-dimensional (3D) microenvironments and specific growth factors motivate the differentiation of human retinal pigment epithelial (hRPE) cells toward a retinal neural lineage. In this study, we evaluated alginate/gelatin (A/G) as a substrate for the culture of hRPE cells.
METHODS
hRPE cells were isolated from neonatal human cadaver globes and cultivated on A/G substrate under different culture conditions, including 30% human amniotic fluid (HAF), 10% fetal bovine serum (FBS), and serum-free Dulbecco's modified Eagle's medium/nutrient mixture F-12 (DMEM/F12). The proliferation of cells in different culture conditions was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and a cell proliferation assay. Immunocytochemistry and real-time PCR were performed to evaluate the effect of the substrate on hRPE cell differentiation.
RESULTS
A significant increase in the cell proliferation rate was observed in hRPE cells cultivated on an A/G substrate. Continuous observations demonstrated that hRPE cells formed densely packed, suspended spheroids in DMEM/F12 culture conditions, with dominant transdifferentiation into amacrine cells. Small adherent clusters of hRPE cells in HAF- and FBS-treated cultures represented dedifferentiation toward retinal progenitor cells. These cultures generated amacrine, rod photoreceptors, and bipolar cells.
CONCLUSIONS
These findings indicated that A/G substrate induced neural retinal cell propagation in cultures and would therefore be promising for RPE-based tissue engineering studies.
Topics: Infant, Newborn; Humans; Retinal Pigment Epithelium; Gelatin; Cells, Cultured; Alginates; Cell Differentiation; Retinal Pigments; Epithelial Cells
PubMed: 36601411
DOI: No ID Found -
Molecules (Basel, Switzerland) Jun 2021Dietary polyphenols are a group of natural compounds that have been proposed to have beneficial effects on human health. They were first known for their antioxidant... (Review)
Review
Dietary polyphenols are a group of natural compounds that have been proposed to have beneficial effects on human health. They were first known for their antioxidant properties, but several studies over the years have shown that these compounds can exert protective effects against chronic diseases. Nonetheless, the mechanisms underlying these potential benefits are still uncertain and contradictory effects have been reported. In this review, we analyze the potential effects of polyphenol compounds on some visual diseases, with a special focus on retinal degenerative diseases. Current effective therapies for the treatment of such retinal diseases are lacking and new strategies need to be developed. For this reason, there is currently a renewed interest in finding novel ligands (or known ligands with previously unexpected features) that could bind to retinal photoreceptors and modulate their molecular properties. Some polyphenols, especially flavonoids (e.g., quercetin and tannic acid), could attenuate light-induced receptor damage and promote visual health benefits. Recent evidence suggests that certain flavonoids could help stabilize the correctly folded conformation of the visual photoreceptor protein rhodopsin and offset the deleterious effect of retinitis pigmentosa mutations. In this regard, certain polyphenols, like the flavonoids mentioned before, have been shown to improve the stability, expression, regeneration and folding of rhodopsin mutants in experimental in vitro studies. Moreover, these compounds appear to improve the integration of the receptor into the cell membrane while acting against oxidative stress at the same time. We anticipate that polyphenol compounds can be used to target visual photoreceptor proteins, such as rhodopsin, in a way that has only been recently proposed and that these can be used in novel approaches for the treatment of retinal degenerative diseases like retinitis pigmentosa; however, studies in this field are limited and further research is needed in order to properly characterize the effects of these compounds on retinal degenerative diseases through the proposed mechanisms.
Topics: Drug Discovery; Gene Expression Regulation; Humans; Photoreceptor Cells, Vertebrate; Polyphenols; Retinal Degeneration; Retinal Pigments
PubMed: 34199888
DOI: 10.3390/molecules26113407 -
Annual Review of Vision Science Sep 2023We live on a planet that is bathed in daily and seasonal sunlight cycles. In this context, terrestrial life forms have evolved mechanisms that directly harness light... (Review)
Review
We live on a planet that is bathed in daily and seasonal sunlight cycles. In this context, terrestrial life forms have evolved mechanisms that directly harness light energy (plants) or decode light information for adaptive advantage. In animals, the main light sensors are a family of G protein-coupled receptors called opsins. Opsin function is best described for the visual sense. However, most animals also use opsins for extraocular light sensing for seasonal behavior and camouflage. While it has long been believed that mammals do not have an extraocular light sensing capacity, recent evidence suggests otherwise. Notably, encephalopsin (OPN3) and neuropsin (OPN5) are both known to mediate extraocular light sensing in mice. Examples of this mediation include photoentrainment of circadian clocks in skin (by OPN5) and acute light-dependent regulation of metabolic pathways (by OPN3 and OPN5). This review summarizes current findings in the expanding field of extraocular photoreception and their relevance for human physiology.
Topics: Mice; Humans; Animals; Opsins; Rod Opsins; Skin; Mammals; Membrane Proteins
PubMed: 37196422
DOI: 10.1146/annurev-vision-100820-094018 -
Molecular Vision 2023Myopia, or nearsightedness, is the most common form of refractive error and is increasing in prevalence. While significant efforts have been made to identify genetic...
PURPOSE
Myopia, or nearsightedness, is the most common form of refractive error and is increasing in prevalence. While significant efforts have been made to identify genetic variants that predispose individuals to myopia, these variants are believed to account for only a small portion of the myopia prevalence, leading to a feedback theory of emmetropization, which depends on the active perception of environmental visual cues. Consequently, there has been renewed interest in studying myopia in the context of light perception, beginning with the opsin family of G-protein coupled receptors (GPCRs). Refractive phenotypes have been characterized in every opsin signaling pathway studied, leaving only Opsin 3 (OPN3), the most widely expressed and blue-light sensing noncanonical opsin, to be investigated for function in the eye and refraction.
METHODS
expression was assessed in various ocular tissues using an Opn3eGFP reporter. Weekly refractive development in retinal and germline mutants from 3 to 9 weeks of age was measured using an infrared photorefractor and spectral domain optical coherence tomography (SD-OCT). Susceptibility to lens-induced myopia was then assessed using skull-mounted goggles with a -30 diopter experimental and a 0 diopter control lens. Mouse eye biometry was similarly tracked from 3 to 6 weeks. A myopia gene expression signature was assessed 24 h after lens induction for germline mutants to further assess myopia-induced changes.
RESULTS
was found to be expressed in a subset of retinal ganglion cells and a limited number of choroidal cells. Based on an assessment of mutants, the OPN3 germline, but not retina conditional knockout, exhibits a refractive myopia phenotype, which manifests in decreased lens thickness, shallower aqueous compartment depth, and shorter axial length, atypical of traditional axial myopias. Despite the short axial length, null eyes demonstrate normal axial elongation in response to myopia induction and mild changes in choroidal thinning and myopic shift, suggesting that susceptibility to lens-induced myopia is largely unchanged. Additionally, the null retinal gene expression signature in response to induced myopia after 24 h is distinct, with opposing , , and polarity compared to controls.
CONCLUSIONS
The data suggest that an OPN3 expression domain outside the retina can control lens shape and thus the refractive performance of the eye. Prior to this study, the role of in the eye had not been investigated. This work adds OPN3 to the list of opsin family GPCRs that are implicated in emmetropization and myopia. Further, the work to exclude retinal OPN3 as the contributing domain in this refractive phenotype is unique and suggests a distinct mechanism when compared to other opsins.
Topics: Animals; Mice; Myopia; Refraction, Ocular; Refractive Errors; Retina; Opsins; Rod Opsins
PubMed: 37287644
DOI: No ID Found -
Annual Review of Entomology Jan 2021Color vision is widespread among insects but varies among species, depending on the spectral sensitivities and interplay of the participating photoreceptors. The... (Review)
Review
Color vision is widespread among insects but varies among species, depending on the spectral sensitivities and interplay of the participating photoreceptors. The spectral sensitivity of a photoreceptor is principally determined by the absorption spectrum of the expressed visual pigment, but it can be modified by various optical and electrophysiological factors. For example, screening and filtering pigments, rhabdom waveguide properties, retinal structure, and neural processing all influence the perceived color signal. We review the diversity in compound eye structure, visual pigments, photoreceptor physiology, and visual ecology of insects. Based on an overview of the current information about the spectral sensitivities of insect photoreceptors, covering 221 species in 13 insect orders, we discuss the evolution of color vision and highlight present knowledge gaps and promising future research directions in the field.
Topics: Animals; Biological Evolution; Color Vision; Compound Eye, Arthropod; Insecta; Photoreceptor Cells, Invertebrate; Retinal Pigments; Spatial Behavior
PubMed: 32966103
DOI: 10.1146/annurev-ento-061720-071644 -
Biochimica Et Biophysica Acta.... Oct 2023The catabolic process of autophagy is arousing the attention of researchers studying diabetic retinopathy (DR), but the role and molecular mechanism of autophagy in DR...
OBJECTIVE
The catabolic process of autophagy is arousing the attention of researchers studying diabetic retinopathy (DR), but the role and molecular mechanism of autophagy in DR are still unclear.
METHODS
An in vivo diabetic rat model and in vitro hyperglycemic-exposed retinal pigment epithelium (RPE) cell cultures were established to mimic early DR. Transmission electron microscopy and mRFP-GFP-LC3 adenovirus transfection were applied for autophagic flux analysis. MicroRNA (miR)-19a-3p, members of the phosphate and tensin homolog (PTEN)/Akt/mammalian target of rapamycin (mTOR) pathway, and the autophagy-related proteins light chain (LC)3II/I and p62 were detected. Annexin V, transwell, Cell Counting Kit-8, fluorescein isothiocyanate-dextran monolayer permeability assay, and transepithelial electrical resistance were performed to evaluate the effects of regulating autophagy on RPE cells under the DR condition.
RESULTS
Autophagy was aberrantly activated in DR as evidenced by autophagosome accumulation. Further mechanistic experiments revealed that DR induced PTEN expression, thus inhibiting Akt/mTOR phosphorylation and stimulating aberrant autophagy and apoptosis. Notably, these events could be reversed by miR-19a-3p directly targeting PTEN. Downregulation of autophagy by miR-19a-3p overexpression, PTEN knockdown, or 3-methyladenine (3-MA) treatment inhibited autophagosome formation and thus effectively ameliorated hyperglycemia-induced RPE cell apoptosis, increased migration, inhibited viability, and enhanced monolayer permeability under the DR condition.
CONCLUSIONS
Our findings suggest that upregulation of miR-19a-3p inhibits aberrant autophagy by directly targeting PTEN, thus protecting RPE cells against DR damage. miR-19a-3p may represent a novel therapeutic target for inducing protective autophagy in early DR.
Topics: Animals; Rats; Autophagy; Diabetic Retinopathy; Epithelial Cells; Mammals; MicroRNAs; Proto-Oncogene Proteins c-akt; Retinal Pigments; Signal Transduction; TOR Serine-Threonine Kinases
PubMed: 37393018
DOI: 10.1016/j.bbamcr.2023.119530 -
Archivum Immunologiae Et Therapiae... Aug 2023Chronic hyperglycemia involves persistent high-glucose exposure and correlates with retinal degeneration. It causes various diseases, including diabetic retinopathy...
Chronic hyperglycemia involves persistent high-glucose exposure and correlates with retinal degeneration. It causes various diseases, including diabetic retinopathy (DR), a major cause of adult vision loss. Most in vitro studies have investigated the damaging short-term effects of high glucose exposure on retinal pigment epithelial (RPE) cells. DR is also a severe complication of diabetes. In this study, we established a model with prolonged high-glucose exposure (15 and 75 mM exogenous glucose for two months) to mimic RPE tissue pathophysiology in patients with hyperglycemia. Prolonged high-glucose exposure attenuated glucose uptake and clonogenicity in ARPE-19 cells. It also significantly increased reactive oxygen species levels and decreased antioxidant protein (superoxide dismutase 2) levels in RPE cells, possibly causing oxidative stress and DNA damage and impairing proliferation. Western blotting showed that autophagic stress, endoplasmic reticulum stress, and genotoxic stress were induced by prolonged high-glucose exposure in RPE cells. Despite a moderate apoptotic cell population detected using the Annexin V-staining assay, the increases in the senescence-associated proteins p53 and p21 and SA-β-gal-positive cells suggest that prolonged high-glucose exposure dominantly sensitized RPE cells to premature senescence. Comprehensive next-generation sequencing suggested that upregulation of oxidative stress and DNA damage-associated pathways contributed to stress-induced premature senescence of ARPE-19 cells. Our findings elucidate the pathophysiology of hyperglycemia-associated retinal diseases and should benefit the future development of preventive drugs. Prolonged high-glucose exposure downregulates glucose uptake and oxidative stress by increasing reactive oxygen species (ROS) production through regulation of superoxide dismutase 2 (SOD2) expression. Autophagic stress, ER stress, and DNA damage stress (genotoxic stress) are also induced by prolonged high-glucose exposure in RPE cells. Consequently, multiple stresses induce the upregulation of the senescence-associated proteins p53 and p21. Although both apoptosis and premature senescence contribute to high glucose exposure-induced anti-proliferation of RPE cells, the present work shows that premature senescence rather than apoptosis is the dominant cause of RPE degeneration, eventually leading to the pathogenesis of DR.
Topics: Adult; Humans; Reactive Oxygen Species; Tumor Suppressor Protein p53; Oxidative Stress; Hyperglycemia; Autophagy; Epithelial Cells; Retinal Pigments
PubMed: 37638991
DOI: 10.1007/s00005-023-00686-9 -
Molecules (Basel, Switzerland) Aug 2023Rods and cones are the photoreceptor cells containing the visual pigment proteins that initiate visual phototransduction following the absorption of a photon. Photon... (Review)
Review
Rods and cones are the photoreceptor cells containing the visual pigment proteins that initiate visual phototransduction following the absorption of a photon. Photon absorption induces the photochemical transformation of a visual pigment, which results in the sequential formation of distinct photo-intermediate species on the femtosecond to millisecond timescales, whereupon a visual electrical signal is generated and transmitted to the brain. Time-resolved spectroscopic studies of the rod and cone photo-intermediaries enable the detailed understanding of initial events in vision, namely the key differences that underlie the functionally distinct scotopic (rod) and photopic (cone) visual systems. In this paper, we review our recent ultrafast (picoseconds to milliseconds) transient absorption studies of rod and cone visual pigments with a detailed comparison of the transient molecular spectra and kinetics of their respective photo-intermediaries. Key results include the characterization of the porphyropsin (carp fish rhodopsin) and human green-cone opsin photobleaching sequences, which show significant spectral and kinetic differences when compared against that of bovine rhodopsin. These results altogether reveal a rather strong interplay between the visual pigment structure and its corresponding photobleaching sequence, and relevant outstanding questions that will be further investigated through a forthcoming study of the human blue-cone visual pigment are discussed.
Topics: Animals; Cattle; Humans; Rhodopsin; Kinetics; Retinal Cone Photoreceptor Cells; Vision, Ocular
PubMed: 37570798
DOI: 10.3390/molecules28155829