Retinol dehydrogenases: Membrane-bound enzymes for the visual function

2014 ◽  
Vol 92 (6) ◽  
pp. 510-523 ◽  
Author(s):  
Mustapha Lhor ◽  
Christian Salesse
Keyword(s):  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Membrane Binding ◽  
Large Family ◽  
Structural Features ◽  
Visual Cycle ◽  
Retinoid Metabolism ◽  
Current State ◽  
Membrane Bound ◽  
Membrane Bound Enzymes

Retinoid metabolism is important for many physiological functions, such as differenciation, growth, and vision. In the visual context, after the absorption of light in rod photoreceptors by the visual pigment rhodopsin, 11-cis retinal is isomerized to all-trans retinal. This retinoid subsequently undergoes a series of modifications during the visual cycle through a cascade of reactions occurring in photoreceptors and in the retinal pigment epithelium. Retinol dehydrogenases (RDHs) are enzymes responsible for crucial steps of this visual cycle. They belong to a large family of proteins designated as short-chain dehydrogenases/reductases. The structure of these RDHs has been predicted using modern bioinformatics tools, which allowed to propose models with similar structures including a common Rossman fold. These enzymes undergo oxidoreduction reactions, whose direction is dictated by the preference and concentration of their individual cofactor (NAD(H)/NADP(H)). This review presents the current state of knowledge on functional and structural features of RDHs involved in the visual cycle as well as knockout models. RDHs are described as integral or peripheral enzymes. A topology model of the membrane binding of these RDHs via their N- and (or) C-terminal domain has been proposed on the basis of their individual properties. Membrane binding is a crucial issue for these enzymes because of the high hydrophobicity of their retinoid substrates.

scholarly journals Pathophysiological features of the visual cycle, cascade and metabolic pathways in retinitis pigmentosa

2021 ◽  
Vol 14 (1) ◽  
pp. 80-88
Author(s):  
M. E. Weener ◽  
D. S. Atarshchikov ◽  
V. V. Kadyshev ◽  
I. V. Zolnikova ◽  
A. M. Demchinsky ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Literature Review ◽  
Retinitis Pigmentosa ◽  
Metabolic Pathways ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Visual Signal ◽  
Visual Cycle ◽  
Target Treatment ◽  
Interphotoreceptor Matrix

This literature review offers a detailed description of the genes and proteins involved in pathophysiological processes in isolated retinitis pigmentosa (RP). To date, 84 genes and 7 candidate genes have been described for non-syndromic RP. Each of these genes encodes a protein that plays a role in vital processes in the retina and / or retinal pigment epithelium, including the cascade of phototransduction (transmission of the visual signal), the visual cycle, ciliary transport, the environment of photoreceptor cilia and the interphotoreceptor matrix. The identification and study of pathophysiological pathways affected in non-syndromic RP is important for understanding the main pathogenic ways and developing approaches to target treatment.

scholarly journals Evolution of the visual cycle: the role of retinoid-binding proteins

2002 ◽  
Vol 175 (1) ◽  
pp. 75-88 ◽  
Author(s):  
F Gonzalez-Fernandez
Keyword(s):  
Binding Proteins ◽  
Binding Protein ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Future Research ◽  
Visual Cycle ◽  
Hormone Binding ◽  
Evolutionary Context ◽  
And Function

The trafficking of retinoids in the retina represents a model to study soluble hormone-binding proteins in a complex system subject to profound evolutionary adaptations. Although a remarkable illustration of convergent evolution, all visual systems detect light in the same way, that is through the photoisomerization of an 11-cis retinoid to a corresponding trans isomer. What is strikingly different between the systems, is the mechanism by which the 11-cis chromophore is reformed and visual pigment regenerated in a process known as the visual cycle. The variations of the cycle address a problem inherent to retinoids themselves. That is, the properties that make these molecules suited for light detection also account for their susceptibility to oxidative and isomeric degradation, and cellular toxicity. The cycle therefore provides an opportunity to examine the role of soluble hormone-binding proteins within an integrative and evolutionary context. The present review focuses on interphotoreceptor retinoid-binding protein (IRBP), a controversial glycolipoprotein that recruits a protein fold common to Cterminal-processing proteases and the crotonase family. This unorthodox retinoid-binding protein is entrapped in the subretinal compartment of those eyes that translocate visual cycle retinoids between the photoreceptors and the retinal pigment epithelium. Recent studies suggest that we should look beyond a strictly carrier function if we are to appreciate the role of IRBP in the visual cycle. Here we draw lessons from other soluble hormone-binding proteins to anticipate avenues of future research likely to provide insight into the structure and function of IRBP in vision.

Studies on the eyes of catfishes with special reference to the tapetum lucidum

1974 ◽  
Vol 186 (1082) ◽  
pp. 13-36 ◽  
Keyword(s):  
Ictalurus Punctatus ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Single Layer ◽  
High Refractive Index ◽  
Extensive Study ◽  
Rods And Cones ◽  
Light Yellow ◽  
Membrane Bound ◽  
Pigment Epithelial Cells

Marine catfishes (Ariidae) and freshwater catfishes (Ictaluridae) have ocular tapeta lucida. Species examined were Bagre marinus (Mitchill), Arius felis (L.), Ictalurus punctatus (Rafinesque), I. natalis (Lesueur), I. nebulosus (Lesueur) and Pylodictis olivaris (Rafinesque). The tapeta are white reflectors located in the pigment epithelium; they occupy most of the fundus except for a narrow black ventral field. A more extensive study was made of the tapetum of the hardhead catfish A. felis . In histologic sections the tapetum is yellow brown and is easily confused with retinal pigment. It can be distinguished because it stains with ferric-ferricyanide and dissolves in methanol-hydrochloric acid after Carnoy fixation. The tapetum is occluded by melanosomes which move inwards in light, and it is exposed by movement outwards of melanosomes in dim light or darkness. Electron microscopy shows that processes of the pigment epithelial cells contain many membrane-bound tapetal spheres which enclose the tapetal pigment and are responsible for reflexion of light. Spheres are 370 nm in diameter (average); there are about 5.5 spheres in 1 μm 3 , and the tapetum is about 90 μm thick. Rods and cones are equal in number; rods form a single layer, cones are single and possess an accessory outer segment. Transmission of the tapetum is minimal at short wavelengths and rises steadily above 500 nm. Reflectance is diffuse; it rises to a maximum at 500 nm, and is high at long wavelengths. The tapetum has a high refractive index, ca . 1.56, favouring light scattering. Some characteristics of the extracted tapetal pigment are pre­sented: it is light yellow, and absorbance maxima occur at 260 and 330 nm in acidic meth­anol. The pigment epithelium contains lysosome-like bodies but no myeloid bodies. The hardhead retina contains a visual pigment 527 2 . Measurements of natural light (irradiance) in coastal waters inhabited by sea catfishes are presented: the waters are turbid and transmit maximally at 575 to 580 nm. The findings, in relation to earlier work on the catfish eye, performance of the eye and habits of the fish are discussed.

scholarly journals Retinoid metabolism in cultured human retinal pigment epithelium

1988 ◽  
Vol 250 (2) ◽  
pp. 459-465 ◽  
Author(s):  
S R Das ◽  
P Gouras
Keyword(s):  
Fatty Acid ◽  
Culture Medium ◽  
Cultured Cells ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Primary Cultures ◽  
Retinyl Palmitate ◽  
Lipid Binding ◽  
Retinoid Metabolism ◽  
Hydrolysis Of

Uptake, esterification and release of all-trans-retinol in primary cultures of human retinal epithelium were studied. Cultured cells were supplemented with 3H-labelled 11,12-all-trans-retinol, using fatty-acid-free albumin as the carrier. This led to incorporation of retinal and the formation of all-trans- and 11-cis-retinyl palmitate. The metabolism of the all-trans ester was monitored in a medium containing various concentrations of foetal-bovine serum (FBS). In 20% (v/v) FBS, the ester was hydrolysed, and all-trans-retinol was released into the culture medium. In the absence of FBS, little ester was hydrolysed and no retinol was found in the medium. Dialysed or heat-inactivated FBS or fatty-acid-free albumin was as effective as FBS in provoking ester hydrolysis and retinol release. The concentration-dependency of this effect on FBS was matched by the corresponding concentrations of albumin alone. A linear relationship was also found between interphotoreceptor retinoid-binding protein and retinoid release. Haemoglobin, which does not bind retinoids, is ineffective in this capacity. It is concluded that lipid-binding substances, mainly albumin, in FBS act as acceptors for retinol and drain the cultured cells of this molecule. The release of the retinol is coupled to the hydrolysis of retinyl esters in the cell, so that there is little or no net hydrolysis of ester if there is no acceptor for retinol in the culture medium. This effect explains why cultured human retinal epithelial cells are depleted of their stores of retinoids when maintained in medium supplemented with FBS.

scholarly journals Retinoids in the visual cycle: Role of the retinal G protein-coupled receptor

2020 ◽  
pp. jlr.TR120000850 ◽  
Author(s):  
Elliot H Choi ◽  
Anahita Daruwalla ◽  
Susie Suh ◽  
Henri Leinonen ◽  
Krzysztof Palczewski
Keyword(s):  
G Protein ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Light Sensitivity ◽  
Visual Signal ◽  
Enzymatic Reactions ◽  
Visual Cycle ◽  
Retinal Regeneration ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

Driven by the energy of a photon, the visual pigments in rod and cone photoreceptor cells isomerize 11-cis-retinal to the all-trans configuration. This photochemical reaction initiates the signal transduction pathway that eventually leads to the transmission of a visual signal to the brain and leaves the opsins insensitive to further light stimulation. For the eye to restore light sensitivity, opsins require recharging with 11-cis-retinal. This trans–cis back conversion is achieved through a series of enzymatic reactions composing the retinoid (visual) cycle. Although it is evident that the classical retinoid cycle is critical for vision, the existence of an adjunct pathway for 11-cis-retinal regeneration has been debated for many years. Retinal pigment epithelium (RPE)–retinal G protein-coupled receptor (RGR) has been identified previously as a mammalian retinaldehyde photoisomerase homologous to retinochrome found in invertebrates. Using pharmacological, genetic, and biochemical approaches, researchers have now established the physiological relevance of the RGR in 11-cis-retinal regeneration. The photoisomerase activity of RGR in the RPE and Müller glia explains how the eye can remain responsive in daylight. In this review, we will focus on retinoid metabolism in the eye and visual chromophore regeneration mediated by RGR.  

Studies of the visual cycle in cultured retinal pigment epithelium (RPE)

1992 ◽  
Vol 55 ◽  
pp. 218
Author(s):  
D. Bok ◽  
M. Lloyd ◽  
A. Carlson ◽  
W. O'Day ◽  
P. Bernstein
Keyword(s):  
Retinal Pigment Epithelium ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Visual Cycle

Carbonic Anhydrase Inhibitor with Topical NSAID Therapy to Manage Cystoid Macular Edema in a Case of Gyrate Atrophy

2017 ◽  
Vol 27 (6) ◽  
pp. e179-e183 ◽  
Author(s):  
Elena Piozzi ◽  
Salvatore Alessi ◽  
Silvia Santambrogio ◽  
Giovanni Cillino ◽  
Marco Mazza ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Macular Edema ◽  
Cystoid Macular Edema ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Carbonic Anhydrase Inhibitor ◽  
Gyrate Atrophy ◽  
First Case ◽  
Membrane Bound ◽  
Inflammatory Drugs

Purpose Gyrate atrophy of the choroid and retina (GACR) is a rare chorioretinal dystrophy characterized by a deficiency of the enzyme ornithine aminotransferase, inherited in an autosomal recessive pattern. Case Report We report a case of a 17-year-old girl with GACR, for whom the level of serum ornithine had been reduced by an arginine-restricted diet. The patient was responsive to an association of topical nonsteroidal anti-inflammatory drugs (NSAIDs) and a carbonic anhydrase inhibitor (CAI) to reduce cystoid macular edema (CME). Conclusions The efficacy of topical NSAIDs and systemic CAI association indicates that the imbalance in the distribution of retinal pigment epithelium membrane-bound carbonic anhydrase could play a major role in CME pathogenesis in GACR. To our knowledge, this is the first case of therapy with CAI treatment for GACR-related CME.

Progressive protein aggregation in PRPF31 patient retinal pigment epithelium cells: the mechanism and its reversal through activation of autophagy

2021 ◽  
Author(s):  
Maria Georgiou ◽  
Chunbo Yang ◽  
Robert Atkinson ◽  
Kuan-Ting Pan ◽  
Adriana Buskin ◽  
...  
Keyword(s):  
Waste Disposal ◽  
Cell Function ◽  
Core Protein ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinal Cell ◽  
Visual Cycle ◽  
Nuclear Speckles ◽  
Retinal Cells ◽  
Rpe Cells

Mutations in pre-mRNA processing factor 31 (PRPF31), a core protein of the spliceosomal tri-snRNP complex, cause autosomal-dominant retinitis pigmentosa (adRP). It has remained an enigma why mutations in ubiquitously expressed tri-snRNP proteins result in retina-specific disorders, and so far, the underlying mechanism of splicing factors-related RP is poorly understood. Here, we used iPSC technology to generate retinal organoids and RPE models from three patients with severe and very severe PRPF31-adRP, normal individuals and a CRISPR/Cas9-corrected isogenic control. To fully assess the impacts of PRPF31 mutations, quantitative proteomics analyses of retinal organoids and RPE cells was carried out showing RNA splicing, autophagy and lysosome, unfolded protein response (UPR) and visual cycle-related pathways to be significantly affected. Strikingly, the patient-derived RPE and retinal cells were characterised by the presence of large amounts of cytoplasmic aggregates containing the mutant PRPF31 and misfolded, ubiquitin-conjugated proteins including key visual cycle proteins, which accumulated progressively with time. Mutant PRPF31 variant was not incorporated into splicing complexes, but reduction of PRPF31 wildtype levels led to tri-snRNP assembly defects in Cajal bodies of PRPF31 patient retinal cells with reduced U4/U6 snRNPs and accumulation of U5, smaller nuclear speckles and reduced formation of active spliceosomes giving rise to global splicing dysregulation. Moreover, the impaired waste disposal mechanisms further exacerbated aggregate formation, and targeting these by activating the autophagy pathway using Rapamycin resulted in reduction of cytoplasmic aggregates and improved cell survival. Our data demonstrate that it is the progressive aggregate accumulation that overburdens the waste disposal machinery rather than direct PRPF31-initiated mis-splicing, and thus relieving the RPE cells from insoluble cytoplasmic aggregates presents a novel therapeutic strategy that can be combined with gene therapy studies to fully restore RPE and retinal cell function in PRPF31-adRP patients.

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