Vitamin A receptors in normal and dystrophic human retina

Bergsma, Donald R.; Wiggert, Barbara; Funahashi, Masakazu; Kuwabara, Toichiro; Chader, Gerald J.

doi:10.1038/265066a0

Cited by 35 publications

(9 citation statements)

References 10 publications

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“…The level of such binding is high, and appears to be at least 10-fold higher than in several rat tissues24 or normal human retina. 25 Binding is quite specific in these cells since retinoic acid and…”

Section: Resultsmentioning

confidence: 99%

Retinoid‐binding Proteins of Retina and Retinoblastoma Cells in Culture

Chader

Wiggert

Russell

et al. 1981

Annals of the New York Academy of Sciences

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Vitamin A plays a special role in the visual process. Evidence from George Wald and his collaborators1 and many other laboratories over the years have given us a basic understanding of the "visual cycle," a unique sequence of interactions of the retinoid with the protein opsin in the retinal photoreceptor (FIG. 1). In this process, retinoid in the form of 11-cis-retinal binds to the protein opsin in a dark reaction to form the visual protein, rhodopsin. Light energy initiates the cleavage of the Schiff base linkage between the retinoid and the protein moiety as well as a neurochemical impulse that is transmitted to the brain as a "visual" stimulus. The retinal released by this process may be rebound to the opsin to again form rhodopsin or be isomerized to the trans-form, reduced and transported to the pigment epithelium where is it stored as the retinyl ester until needed again in the photoreceptor visual cycle. Thus, vitamin A and its aldehyde form, retinal, are cycled through a series of complex photosensitive reactions but are conserved in the process much as is a cofactor in an enzymatic reaction. There is little or no net usage or metabolism of the retinoid to nonmetabolically active forms.The more general role that vitamin A and its natural metabolites play in differentiation and maintenance of epithelial tissues, bone tissues, the reproductive system, etc. is less well understood. It is clear however that the vitamin is necessary for such normal development and function since vitamin A deficiency quickly leads to such clinical problems as xerophthalmia,z keratomalacia,3 reproductive failure,4 and debilitation of the immune response.5 Repletion of vitamin A (retinol) and in most cases its natural metabolite, retinoic acid, can reverse many of these effects. Retinoic acid for example when applied topically can reverse the corneal signs of xerophthalmia.6'7As with its general action, the molecular mechanism(s) of vitamin A action are not clear and are probably pleiotropic in nature. Studies on vitamin A-deficient animals indicate that at least one role of retinoid is to act as an intermediate in the cellular biosynthesis of gly~oproteins.8~9 In this process, retinyl phosphate functions as a carrier, transferring sugar moieties (e.g. mannose) across membranes and in the formation of membrane glycoprotein.9 Protein synthesis in rough endoplasmic reticulum is also affected by vitamin A with a difference in amino acid charging of t-RNA in intestinal preparations from normal and vitamin A-deficient animals.8 More recently, it has been shown that liver nuclei of vitamin A-deficient rats show decreased RNA synthesis and smaller sized nascent RNA segments when compared to nuclei isolated from retinolrepleted control animals.10 Retinoic acid has also been implicated in control of transcriptional events in the nucleus, specifically in the control of interferon synthesis in cultured cells.11 Thus, it appears that retinoids may directly influence gene expression at the nuclear level.

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Section: Resultsmentioning

confidence: 99%

Retinoid‐binding Proteins of Retina and Retinoblastoma Cells in Culture

Chader

Wiggert

Russell

et al. 1981

Annals of the New York Academy of Sciences

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“…However, the amount of lipofuscin present in Stargardt's disease is 2-5 times that of age-matched controls (Delori et al, 1995). Interestingly, lipofuscin deposits in the RPE have also been seen in cases of AMD and RP (Bergsma et al, 1977;Kliffen et al, 1997;Kolb et al, 1974).…”

Section: Histologymentioning

confidence: 89%

Stargardt's Disease and theABCRGene

Westerfeld

Mukai

2008

Seminars in Ophthalmology

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Stargardt's disease is an autosomal recessive form of juvenile macular degeneration. The clinical presentation, relevant ancillary tests, and classic histologic features will be reviewed. The role of genetic mutations in the pathophysiology of Stargardt's disease will also be explored. Stargardt's disease is caused by mutations in the ABCR (ABCA4) gene on chromosome 1. Mutations in this gene have also been attributed to some cases of cone-rod dystrophy, retinitis pigmentosa, and age-related macular degeneration. The genetic and molecular pathways that produce Stargardt's disease will be discussed. Future diagnostic and therapeutic objectives for this visually disabling condition will also be presented.

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“…We have previously shown that IRBP is synthesized by the primate retina ; several lines of evidence now suggest that IRBP is synthesized specifically in the retinal photoreceptor cells. These include early studies on retinal development and fractionation (Wiggert et al, 1978) and on retinal photoreceptor degeneration (Bergsma et al, 1977). More recently, compelling evidence has been presented that this protein is synthesized by rod photoreceptor cells Hollyfield, 1984;Rodrigues et al, 1985).…”

Section: Discussionmentioning

confidence: 99%

Butyrate enhances the synthesis of interphotoreceptor retinoid‐binding protein (IRBP) by Y‐79 human retinoblastoma cells

Kyritsis

Wiggert

Lee

et al. 1985

Journal Cellular Physiology

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The synthesis and secretion of interphotoreceptor retinoid-binding protein (IRBP) from Y-79 human retinoblastoma cells was investigated using immunocytochemistry and SDS-polyacrylamide gel electrophoresis. Indirect immunofluorescence of cells growing in monolayer culture for 11 and 13 days showed no significant IRBP staining although by SDS-polyacrylamide gel electrophoresis, a small amount of IRBP was detected in the culture medium, suggesting synthesis and extracellular secretion. Butyrate (2mM) treatment of cells starting on the eighth day of culture resulted in a dramatic increase of IRBP fluorescence 3-5 days after treatment. Treatment of cells in all conditions with 1 microM monensin for 3 h showed concentration of IRBP in the Golgi apparatus of about 10-20% of cells as proved by a double immunofluorescent technique, employing anti-IRBP antibody and wheat-germ agglutinin. Incubation of cells with either radiolabeled amino acids or glucosamine followed by analysis of cell cytosol and culture medium by SDS-polyacrylamide gel electrophoresis also confirmed that 1) IRBP is synthesized by the Y-79 cells and secreted into the medium and 2) its production is markedly increased by butyrate treatment. The enhancement of IRBP synthesis by butyrate suggests biochemical differentiation of Y-79 cells possibly into photoreceptor-like cells and offers a new system for studying the properties of this unique retinoid-binding protein and of factors that control its synthesis and secretion.

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Vitamin A receptors in normal and dystrophic human retina

Cited by 35 publications

References 10 publications

Retinoid‐binding Proteins of Retina and Retinoblastoma Cells in Culture

Retinoid‐binding Proteins of Retina and Retinoblastoma Cells in Culture

Stargardt's Disease and theABCRGene

Butyrate enhances the synthesis of interphotoreceptor retinoid‐binding protein (IRBP) by Y‐79 human retinoblastoma cells

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