retinaldehyde and Retinal-Diseases

The visual system produces visual chromophore, 11-

Topics: Alcohol Oxidoreductases; Animals; Ependymoglial Cells; Genetic Predisposition to Disease; Humans; Mutation; Oxidation-Reduction; Phenotype; Retinal Diseases; Retinal Pigment Epithelium; Retinal Rod Photoreceptor Cells; Retinaldehyde; Vision, Ocular; Vitamin A

Topics: Acyltransferases; Animals; cis-trans-Isomerases; Coenzyme A-Transferases; Humans; Mevalonic Acid; Photoreceptor Cells; Retinal Diseases; Retinaldehyde; Retinoids; Retinol-Binding Proteins; Rhodopsin

The visual cycle is a sequential enzymatic reaction for vitamin A, all-trans-retinol, occurring in the outer layer of the human retina and is essential for the maintenance of vision. The central source of retinol is derived from dietary intake of both retinol and pro-vitamin A carotenoids. A series of enzymatic reactions, located in both the photoreceptor outer segment and the retinal pigment epithelium, transform retinol into the visual chromophore 11-cis-retinal, regenerating visual pigments. Retina specific proteins carry out the majority of the visual cycle, and any significant interruption in this sequence of reactions is capable of causing varying degrees of blindness. Among these important proteins are Lecithin:retinol acyltransferase (LRAT) and retinal pigment epithelium-specific 65-kDa protein (RPE65) known to be responsible for esterification of retinol to all-trans-retinyl esters and isomerization of these esters to 11-cis-retinal, respectively. Deleterious mutations in these genes are identified in human retinal diseases that cause blindness, such as Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP). Herein, we discuss the pathology of 11-cis-retinal deficiency caused by these mutations in both animal disease models and human patients. We also review novel therapeutic strategies employing artificial visual chromophore 9-cis-retinoids which have been employed in clinical trials involving LCA patients.

Topics: Acyltransferases; Animals; cis-trans-Isomerases; Clinical Trials as Topic; Disease Models, Animal; Humans; Retina; Retinal Diseases; Retinal Pigments; Retinaldehyde; Vision, Ocular; Vitamin A

A major goal in vision research over the past few decades has been to understand the molecular details of retinoid processing within the retinoid (visual) cycle. This includes the consequences of side reactions that result from delayed all-trans-retinal clearance and condensation with phospholipids that characterize a variety of serious retinal diseases. Knowledge of the basic retinoid biochemistry involved in these diseases is essential for development of effective therapeutics. Photoisomerization of the 11-cis-retinal chromophore of rhodopsin triggers a complex set of metabolic transformations collectively termed phototransduction that ultimately lead to light perception. Continuity of vision depends on continuous conversion of all-trans-retinal back to the 11-cis-retinal isomer. This process takes place in a series of reactions known as the retinoid cycle, which occur in photoreceptor and RPE cells. All-trans-retinal, the initial substrate of this cycle, is a chemically reactive aldehyde that can form toxic conjugates with proteins and lipids. Therefore, much experimental effort has been devoted to elucidate molecular mechanisms of the retinoid cycle and all-trans-retinal-mediated retinal degeneration, resulting in delineation of many key steps involved in regenerating 11-cis-retinal. Three particularly important reactions are catalyzed by enzymes broadly classified as acyltransferases, short-chain dehydrogenases/reductases and carotenoid/retinoid isomerases/oxygenases. This article is part of a Special Issue entitled: Retinoid and Lipid Metabolism.

Topics: Acyltransferases; Alcohol Oxidoreductases; Animals; Carrier Proteins; cis-trans-Isomerases; Eye Proteins; Humans; Mice; Phospholipids; Photoreceptor Cells, Vertebrate; Rats; Retina; Retinal Diseases; Retinaldehyde; Retinoids; Rhodopsin; Vision, Ocular

The lipid phase of the photoreceptor outer segment membrane is essential to the photon capturing and signaling functions of rhodopsin. Rearrangement of phospholipids in the bilayer accompanies the formation of the active intermediates of rhodopsin following photon absorption. Furthermore, evidence for the formation of a condensation product between the photolyzed chromophore all-trans-retinal and phosphatidylethanolamine indicates that phospholipid may also participate in the movement of the retinoid in the membrane. The downside of these interactions is the formation of bisretinoid-phosphatidylethanolamine compounds that accumulate in retinal pigment epithelial cells with age and that are particularly abundant in some retinal disorders. The propensity of these compounds to negatively impact on the cells has been linked to the pathogenesis of some retinal disorders including juvenile onset recessive Stargardt disease and age-related macular degeneration.

Topics: Animals; Humans; Phospholipids; Photoreceptor Cells; Retinal Diseases; Retinal Pigment Epithelium; Retinaldehyde; Retinoids

Knowledge about retinal photoreceptor signal transduction and the visual cycle required for normal eyesight has increased exponentially over the past decade. Substantial progress in human genetics has facilitated the identification of candidate genes and complex networks underlying inherited retinal diseases. Natural mutations in animal models that mimic human diseases have been characterized and advanced genetic manipulation can now be used to generate small mammalian models of human retinal diseases. Pharmacological repair of defective visual processes in animal models not only validates their involvement in vision, but also provides great promise for the development of improved therapies for millions who are progressing towards blindness or are almost completely robbed of their eyesight.

Topics: Animals; Blindness; Drug Delivery Systems; Eye Proteins; Humans; Models, Biological; Photoreceptor Cells, Vertebrate; Retinal Diseases; Retinaldehyde; Retinoids; Vision, Ocular; Visual Perception

Nonsyndromic recessive retinal dystrophies cause severe visual impairment due to the death of photoreceptor and retinal pigment epithelium cells. These diseases until recently have been considered to be incurable. Molecular genetic studies in the last two decades have revealed the underlying molecular causes in approximately two-thirds of patients. The mammalian eye has been at the forefront of therapeutic trials based on gene augmentation in humans with an early-onset nonsyndromic recessive retinal dystrophy due to mutations in the retinal pigment epithelium-specific protein 65kDa (RPE65) gene. Tremendous challenges still lie ahead to extrapolate these studies to other retinal disease-causing genes, as human gene augmentation studies require testing in animal models for each individual gene and sufficiently large patient cohorts for clinical trials remain to be identified through cost-effective mutation screening protocols.

Topics: Animals; Carrier Proteins; Cats; cis-trans-Isomerases; Disease Models, Animal; Dogs; Eye; Eye Proteins; Gene Transfer Techniques; Genes; Genes, Recessive; Genetic Testing; Genetic Therapy; Humans; Lighting; Mice; Mice, Knockout; Mutation; Retina; Retinal Diseases; Retinaldehyde; Transgenes

Retinitis punctata albescens is a form of retinitis pigmentosa characterized by white fleck-like deposits in the fundus, in most cases caused by pathogenic variants in. An 8-year-old Caucasian female has been complaining of nyctalopia for the last 2 years. No other ocular symptoms were present. No relevant past medical or familiar history was described. At clinical examination, the patient's best-corrected visual acuity was 20/20 in both eyes. Anterior segment evaluation and intraocular pressure were normal in both eyes. At fundoscopy, multiple punctate whitish-yellow fleck-like lesions were observed in the proximity of temporal superior and inferior vascular arcades. Scotopic electroretinogram demonstrated severely reduced rod response, without improvement or recovery of rod system function after prolonged dark adaptation. Blood DNA samples of this patient and from her parents were screened for causal variants in. A probable pathogenic frameshift variant was identified in homozygosity in the

Topics: Carrier Proteins; Child; Electroretinography; Female; Humans; Mutation; Retinal Diseases; Retinaldehyde

Topics: Carrier Proteins; Humans; Mutation; Retinal Diseases; Retinaldehyde; Retinitis

This study aimed to evaluate effect of TAU on NMDA-induced changes in retinal redox status, retinal cell apoptosis and retinal morphology in Sprague-Dawley rats. Taurine was injected intravitreally as pre-, co- or post-treatment with NMDA and 7 days post-treatment retinae were processed for estimation of oxidative stress, retinal morphology using H&E staining and retinal cell apoptosis using TUNEL staining. Treatment with TAU, particularly pre-treatment, significantly increased retinal glutathione, superoxide dismutase and catalase levels compared to NMDA-treated rats; whereas, the levels of malondialdehyde reduced significantly. Reduction in retinal oxidative stress in TAU pre-treated group was associated with significantly greater fractional thickness of ganglion cell layer within inner retina and retinal cell density in inner retina. TUNEL staining showed significantly reduced apoptotic cell count in TAU pre-treated group compared to NMDA group. It could be concluded that TAU protects against NMDA-induced retinal injury in rats by reducing retinal oxidative stress.

Topics: Animals; Apoptosis; Excitatory Amino Acid Agonists; Female; Male; N-Methylaspartate; Oxidation-Reduction; Oxidative Stress; Protective Agents; Rats; Rats, Sprague-Dawley; Retinal Diseases; Retinaldehyde; Taurine

We use molecular dynamics (MD) simulations to determine the binding properties of different retinoid species to cellular retinaldehyde binding protein (CRALBP). The complexes formed by 9-cis-retinal or 11-cis-retinal bound to both the native protein and the R234W mutant, associated to Bothnia-retina dystrophy, are investigated. The presented studies are also complemented by analysis of the binding structures of the CRALBP/9-cis-retinol and CRALBP/9,13-dicis-retinal complexes. We find that the poor X-ray scattering properties of the polyene tail of the ligand in all wild-type complexes can be attributed to a high mobility of this region, which does not localize in a single binding conformation even at very low temperatures. Our simulations report a clear difference in the residual solvation pattern in CRALBP complexes with either 9-cis- or 9,13-dicis-retinal. The reported structures indicate that the microsolvation properties of the ligand are the key structural element triggering the very recently discovered isomerase activity of this protein. The binding geometries obtained by MD simulations are validated by calculation of the respective optical spectra by the ZINDO/S semiempirical method, which can reproduce with good qualitative agreement the different red-shifts of the first absorption band of the different complexes.

Topics: Carrier Proteins; Diterpenes; Eye Diseases, Hereditary; Humans; Molecular Dynamics Simulation; Mutation; Protein Conformation; Retinal Diseases; Retinaldehyde

To evaluate phenotypes caused by different RLBP1 mutations in autosomal recessive retinitis pigmentosa of Bothnia type.. Compound heterozygotes for mutations in the RLBP1 gene [c.677T>A]+[c.700C>T] (p.M226K+p.R234W), n = 10, aged 7-84 years, and homozygotes c.677T>A (p.M226K), n = 2, aged 63 and 73 years, were studied using visual acuity (VA), low-contrast VA, visual fields (VFs) and optical coherence tomography (OCT). Retrospective VA and VFs, standardized dark adaptation and full-field electroretinograms (ERGs) were analysed and prolonged dark adaptometry and ERG (at 24 hr) were performed.. Progressive decline of VA and VF areas was age-dependent. Retinal degenerative maculopathy, peripheral degenerative changes and retinitis punctata albescens (RPA) were present. Early retinal thinning in the central foveal, foveal (Ø 1 mm), and inner ring (Ø 3 mm) in the macular region, with homogenous, high-reflectance RPA changes, was visualized in and adjacent to the retinal pigment epithelium/choriocapillaris using OCT. Reduced dark adaptation and affected ERGs were present in all ages. Prolonged dark adaptation and ERG (at 24 hr), an increase in final threshold, and ERG rod and mixed rod/cone responses were found.. The two RLBP1 genotypes presented a phenotypical and electrophysiological expression of progressive retinal disease similar to that previously described in homozygotes for the c.700C>T (p.R234W) RLBP1 mutation. The uniform phenotypical expression of RLBP1 mutations is relevant information for the disease and of importance in planning future treatment strategies.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Carrier Proteins; Child; Databases, Genetic; DNA Mutational Analysis; Electroretinography; Eye Diseases, Hereditary; Female; Fluorescein Angiography; Fundus Oculi; Genetic Association Studies; Humans; Male; Middle Aged; Mutation; Phenotype; Retinal Diseases; Retinaldehyde; Retrospective Studies; Tomography, Optical Coherence; Young Adult

Chronic inflammation is an important component that contributes to many age-related neurodegenerative diseases, including macular degeneration. Here, we report a role for toll-like receptor 3 (TLR3) in cone-rod dystrophy (CORD) of mice lacking ATP-binding cassette transporter 4 (ABCA4) and retinol dehydrogenase 8 (RDH8), proteins critical for all-trans-retinal clearance in the retina. Increased expression of toll-like receptor-signaling elements and inflammatory changes were observed in Rdh8(-/-)Abca4(-/-) eyes by RNA expression analysis. Unlike 3-month-old Rdh8(-/-)Abca4(-/-) mice that developed CORD, 6-month-old Tlr3(-/-)Rdh8(-/-)Abca4(-/-) mice did not evidence an abnormal retinal phenotype. Light-induced retinal degeneration in Tlr3(-/-)Rdh8(-/-)Abca4(-/-) mice was milder than that in Rdh8(-/-)Abca4(-/-) mice, and a 2-fold increased TLR3 expression was detected in light-illuminated retinas of Rdh8(-/-)Abca4(-/-) mice compared with nonilluminated retinas. Poly(I-C), a TLR3 ligand, caused caspase-8-independent cellular apoptosis. Whereas poly(I-C) induced retinal cell death in Rdh8(-/-)Abca4(-/-) and WT mice both in vivo and ex vivo, this was not seen in mice lacking Tlr3. Far fewer invasive macrophage/microglial cells in the subretinal space and weaker activation of Muller glial cells were exhibited by Tlr3(-/-)Rdh8(-/-) Abca4(-/-) mice compared with Rdh8(-/-)Abca4(-/-) mice at 3 and 6 months of age, indicating that loss of TLR3 inhibits local inflammation in the retina. Both poly(I-C) and endogenous products emanating from dying/dead retinal cells induced NF-κB and IRF3 activation. These findings demonstrate that endogenous products from degenerating retina stimulate TLR3 that causes cellular apoptosis and retinal inflammation and that loss of TLR3 protects mice from CORD.

Topics: Alcohol Oxidoreductases; Animals; Apoptosis; ATP-Binding Cassette Transporters; Gene Expression Profiling; Inflammation; Mice; Mice, Knockout; Retinal Degeneration; Retinal Diseases; Retinaldehyde; Toll-Like Receptor 3

Topics: Animals; Fluorescence; Fundus Oculi; Humans; Lipofuscin; Oxidants, Photochemical; Photoreceptor Cells, Vertebrate; Prognosis; Retinal Diseases; Retinal Pigment Epithelium; Retinaldehyde; Retinoids; Spectrometry, Fluorescence

Exposure to bright light can cause visual dysfunction and retinal photoreceptor damage in humans and experimental animals, but the mechanism(s) remain unclear. We investigated whether the retinoid cycle (i.e. the series of biochemical reactions required for vision through continuous generation of 11-cis-retinal and clearance of all-trans-retinal, respectively) might be involved. Previously, we reported that mice lacking two enzymes responsible for clearing all-trans-retinal, namely photoreceptor-specific ABCA4 (ATP-binding cassette transporter 4) and RDH8 (retinol dehydrogenase 8), manifested retinal abnormalities exacerbated by light and associated with accumulation of diretinoid-pyridinium-ethanolamine (A2E), a condensation product of all-trans-retinal and a surrogate marker for toxic retinoids. Now we show that these mice develop an acute, light-induced retinopathy. However, cross-breeding these animals with lecithin:retinol acyltransferase knock-out mice lacking retinoids within the eye produced progeny that did not exhibit such light-induced retinopathy until gavaged with the artificial chromophore, 9-cis-retinal. No significant ocular accumulation of A2E occurred under these conditions. These results indicate that this acute light-induced retinopathy requires the presence of free all-trans-retinal and not, as generally believed, A2E or other retinoid condensation products. Evidence is presented that the mechanism of toxicity may include plasma membrane permeability and mitochondrial poisoning that lead to caspase activation and mitochondria-associated cell death. These findings further understanding of the mechanisms involved in light-induced retinal degeneration.

Topics: Acute Disease; Aging; Alcohol Oxidoreductases; Animals; Apoptosis; ATP-Binding Cassette Transporters; bcl-2-Associated X Protein; Caspases; Cell Line; Cell Survival; Chromatography, High Pressure Liquid; Chromatography, Liquid; Diterpenes; Ethanolamine; Humans; Light; Mass Spectrometry; Mice; Oxidation-Reduction; Rats; Retina; Retinal Degeneration; Retinal Diseases; Retinaldehyde; Retinyl Esters; Rhodopsin; Vitamin A

RPE65 is a retinal pigment epithelial protein essential for the regeneration of 11-cis-retinal, the chromophore of cone and rod visual pigments. Mutations in RPE65 lead to a spectrum of retinal dystrophies ranging from Leber's congenital amaurosis to autosomal recessive retinitis pigmentosa. One of the most frequent missense mutations is an amino acid substitution at position 91 (R91W). Affected patients have useful cone vision in the first decade of life, but progressively lose sight during adolescence. We generated R91W knock-in mice to understand the mechanism of retinal degeneration caused by this aberrant Rpe65 variant. We found that in contrast to Rpe65 null mice, low but substantial levels of both RPE65 and 11-cis-retinal were present. Whereas rod function was impaired already in young animals, cone function was less affected. Rhodopsin metabolism and photoreceptor morphology were disturbed, leading to a progressive loss of photoreceptor cells and retinal function. Thus, the consequences of the R91W mutation are clearly distinguishable from an Rpe65 null mutation as evidenced by the production of 11-cis-retinal and rhodopsin as well as by less severe morphological and functional disturbances at early age. Taken together, the pathology in R91W knock-in mice mimics many aspects of the corresponding human blinding disease. Therefore, this mouse mutant provides a valuable animal model to test therapeutic concepts for patients affected by RPE65 missense mutations.

Topics: Age of Onset; Animals; Carrier Proteins; cis-trans-Isomerases; Eye Proteins; Humans; Mice; Mutation, Missense; Photoreceptor Cells; Point Mutation; Retinal Diseases; Retinaldehyde

Retinol dehydrogenase 12 (RDH12) is an NADP(+)-dependent oxidoreductase that in vitro catalyzes the reduction of all-trans-retinaldehyde to all-trans-retinol or the oxidation of retinol to retinaldehyde depending on substrate and cofactor availability. Recent studies have linked the mutations in RDH12 to severe early-onset autosomal recessive retinal dystrophy. The biochemical basis of photoreceptor cell death caused by mutations in RDH12 is not clear because the physiological role of RDH12 is not yet fully understood. Here we demonstrate that, although bi-directional in vitro, in living cells, RDH12 acts exclusively as a retinaldehyde reductase, shifting the retinoid homeostasis toward the increased levels of retinol and decreased levels of bioactive retinoic acid. The retinaldehyde reductase activity of RDH12 protects the cells from retinaldehyde-induced cell death, especially at high retinaldehyde concentrations, and this protective effect correlates with the lower levels of retinoic acid in RDH12-expressing cells. Disease-associated mutants of RDH12, T49M and I51N, exhibit significant residual activity in vitro, but are unable to control retinoic acid levels in the cells because of their dramatically reduced affinity for NADPH and much lower protein expression levels. These results suggest that RDH12 acts as a regulator of retinoic acid biosynthesis and protects photoreceptors against overproduction of retinoic acid from all-trans-retinaldehyde, which diffuses into the inner segments of photoreceptors from illuminated rhodopsin. These results provide a novel insight into the mechanism of retinal degeneration associated with mutations in RDH12 and are consistent with the observation that RDH12-null mice are highly susceptible to light-induced retinal apoptosis in cone and rod photoreceptors.

Topics: Alcohol Oxidoreductases; Amino Acid Substitution; Animals; Apoptosis; Gene Expression Regulation, Enzymologic; Genetic Diseases, Inborn; Homeostasis; Humans; Light; Macaca mulatta; Mice; Mice, Mutant Strains; Mutation, Missense; NADP; Oxidation-Reduction; Photoreceptor Cells; Retinal Diseases; Retinaldehyde; Rhodopsin; Tretinoin

Cellular retinaldehyde-binding protein (CRALBP) is an essential protein in the human visual cycle without a known three-dimensional structure. Previous studies associate retinal pathologies to specific mutations in the CRALBP protein. Here we use homology modeling and molecular dynamics methods to investigate the structural mechanisms by which CRALBP functions in the visual cycle. We have constructed two conformations of CRALBP representing two states in the process of ligand association and dissociation. Notably, our homology models map the pathology-associated mutations either directly in or adjacent to the putative ligand-binding cavity. Furthermore, six novel residues have been identified to be crucial for the hinge movement of the lipid-exchange loop in CRALBP. We conclude that the binding and release of retinoid involve large conformational changes in the lipid-exchange loop at the entrance of the ligand-binding cavity.

Topics: Amino Acid Sequence; Binding Sites; Carrier Proteins; Humans; Ligands; Lipids; Models, Molecular; Molecular Sequence Data; Motion; Mutation; Protein Conformation; Retinal Diseases; Retinaldehyde; Sequence Alignment; Structural Homology, Protein

The natural ligand of the retinal photoreceptor rhodopsin, 11-cis-retinal, is isomerized to its all-trans configuration as a consequence of light absorption in the first step of the visual phototransduction process. Here we show, by means of difference spectroscopy and high-performance liquid chromatography analysis, that thermal denaturation of rhodopsin induces the same type of isomerization. This effect is likely due to thermally induced conformational rearrangements of amino acid residues in the retinal-binding pocket--possibly implying helical movements--and highlights the tight coupling between 11-cis-retinal and opsin. This effect could have implications in the instability and functional changes seen for certain mutations in rhodopsin associated with retinal disease, and in the stability of the different conformers induced by mutations in other G protein-coupled receptors.

Topics: Animals; Cattle; Chromatography, High Pressure Liquid; Hot Temperature; Night Blindness; Protein Denaturation; Receptors, G-Protein-Coupled; Retinal Diseases; Retinaldehyde; Rhodopsin; Spectrum Analysis; Stereoisomerism

Mutations in the gene encoding 11-cis-retinol dehydrogenase (RDH5; EC ) are associated with fundus albipunctatus, an autosomal recessive eye disease characterized by stationary night blindness and accumulation of white spots in the retina. In addition, some mutated alleles are associated with development of cone dystrophy, especially in elderly patients. The numbers of identified RDH5 mutations linked to fundus albipunctatus have increased considerably during recent years. In this work, we have characterized the biochemical and cell biological properties of 11 mutants of RDH5 to understand the molecular pathology of the disease. All RDH5 mutants showed decreased protein stability and subcellular mislocalization and, in most cases, loss of enzymatic activity in vitro and in vivo. Surprisingly, mutant A294P displays significant enzymatic activity. Cross-linking studies and molecular modeling showed that RDH5 is dimeric, and co-expression analyses of wild-type and mutated alleles showed that the mutated enzymes, in a trans-dominant-negative manner, influenced the in vivo enzymatic properties of functional variants of the enzyme, particularly the A294P mutant. Thus, under certain conditions, nonfunctional alleles act in a dominant-negative way on functional but relatively unstable mutated alleles. However, in heterozygous individuals carrying one wild-type allele, the disease is recessive, probably due to the stability of the wild-type enzyme.

Topics: Alcohol Oxidoreductases; Animals; Carrier Proteins; Cell Fractionation; Chromatography, High Pressure Liquid; COS Cells; Cross-Linking Reagents; Genes, Reporter; Humans; Immunohistochemistry; Microsomes; Models, Molecular; Mutation; Protein Structure, Tertiary; Retinal Diseases; Retinaldehyde; Transfection; Vitamin A

Retinol dehydrogenase (RDH), the enzyme that catalyzes the reduction of all-trans-retinal to all-trans-retinol within the photoreceptor outer segment, was the first visual cycle enzymatic activity to be identified. Previous work has shown that this enzyme utilizes NADPH, shows a marked preference for all-trans-retinal over 11-cis-retinal, and is tightly associated with the outer segment membrane. This paper reports the identification of a novel member of the short chain dehydrogenase/reductase family, photoreceptor RDH (prRDH), using subtraction and normalization of retina cDNA, high throughput sequencing, and data base homology searches to detect retina-specific genes. Bovine and human prRDH are highly homologous and are most closely related to 17-beta-hydroxysteroid dehydrogenase 1. The enzymatic properties of recombinant bovine prRDH closely match those previously reported for RDH activity in crude bovine rod outer segment preparations. In situ hybridization and RNA blotting show that the PRRDH gene is expressed specifically in photoreceptor cells, and protein blotting and immunocytochemistry show that prRDH localizes exclusively to both rod and cone outer segments and that prRDH is tightly associated with outer segment membranes. Taken together, these data indicate that prRDH is the enzyme responsible for the reduction of all-trans-retinal to all-trans-retinol within the photoreceptor outer segment.

Topics: Alcohol Oxidoreductases; Amino Acid Sequence; Animals; Cattle; Cell Membrane; Humans; Molecular Sequence Data; NAD; Retinal Diseases; Retinaldehyde; Rod Cell Outer Segment; Vitamin A

Surgically resected subretinal proliferative tissue (SRP) in proliferative vitreoretinopathy was examined by morphological and immunohistochemical methods. Membranous and strand-like SRPs were observed. Membranous SRP (4 cases) consisted of retinal pigment epithelial cells (RPEs) and a thin layer of extracellular materials. Strand-like SRP (14 cases) had a core, in which the proliferated cells were embedded among extracellular materials. RPEs and glial cells were found on the surface of the core. Immunohistochemical investigation revealed that the predominant cell components of the strand-like SRPs were RPEs and Müller cells, whereas membranous SRPs were composed mainly of RPEs. It was found that the majority of membranous and strand-like SRPs contained types I, III and IV collagens and fibronectin in the extracellular space. Based on the results of this study, a hypothetical process for the formation of SRP tissues was proposed.

Topics: Animals; Carrier Proteins; Extracellular Matrix; Eye Diseases; Glial Fibrillary Acidic Protein; Humans; Immunoenzyme Techniques; Pigment Epithelium of Eye; Rats; Rats, Inbred Strains; Retinal Detachment; Retinal Diseases; Retinaldehyde; Vitreous Body

Topics: Acetylcholine; Choline; Embolism; Humans; Peripheral Vascular Diseases; Retinal Artery Occlusion; Retinal Diseases; Retinaldehyde

Topics: Humans; Hyperlipidemias; Retina; Retinal Diseases; Retinaldehyde

Topics: Embolism; Humans; Retinal Artery; Retinal Diseases; Retinaldehyde

Topics: Arteriosclerosis; Humans; Retina; Retinal Diseases; Retinaldehyde

Topics: Cell Differentiation; Embolism; Endarteritis; Humans; Peripheral Vascular Diseases; Retinal Artery; Retinal Diseases; Retinaldehyde