Disease relevance of RPE65

• The identification of RPE65 as the visual cycle target for the retinoic acids makes it feasible to develop useful drugs to treat retinal and macular degeneration while avoiding the substantial side effects of the retinoic acids [1].
• It is shown here by using a quantitative fluorescence technique, that Accutane (13-cis-retinoic acid), a drug used in the treatment of acne but that causes night blindness, binds to RPE65 with a K(D) of 195 nM [1].
• METHODS: Rats of four inbred strains (Lewis, Brown Norway, Fischer, and SHR) were immunized with native or recombinant bovine RPE65, or with S-antigen (S-Ag), emulsified with complete Freund adjuvant, and treated simultaneously with killed Bordetella pertussis bacteria, as indicated [2].

High impact information on RPE65

• RPE65 is essential for the biosynthesis of 11-cis-retinal, the chromophore of rhodopsin [3].
• The specific binding of retinoic acid to RPE65 and approaches to the treatment of macular degeneration [1].
• The binding of the retinoic acids to RPE65 is competitive with all-trans-retinyl ester binding, and this competition inhibits visual cycle function [1].
• A retinoic acid analog that binds weakly to RPE65 is not inhibitory [1].
• These RPE65 antagonists block regeneration of 11-cis-retinal, the chromophore of rhodopsin, thereby demonstrating that RPE65 is at least partly rate-limiting in the visual cycle [4].

Biological context of RPE65

• We compared the levels of translation products and mRNA stability among RPE65 transcripts containing deletions of the 5'- and 3'-UTRs [5].

Anatomical context of RPE65

• Treatment of crude bovine RPE membranes with (3R)-3-[boc-lys(biotinyl)-O]-all-trans-retinol chloroacetate 1 in the low micromolar range led to the specific labeling of RPE65 and lecithin retinol acyltransferase (LRAT) [6].
• RPE65 is a major membrane associated protein found in the vertebrate retinal pigment epithelium (RPE) [7].
• Identification of the RPE65 protein in mammalian cone photoreceptors [8].

Associations of RPE65 with chemical compounds

• A cleavable affinity biotinylating agent reveals a retinoid binding role for RPE65 [6].
• These quantitative experiments are performed by measuring the quenching of RPE65 fluorescence by added tRP [9].
• Previous studies have also shown that RPE65 is specifically labeled with all-trans-retinyl ester based affinity labeling agents, suggesting a retinyl ester binding role for the protein [9].
• In the present work, we show that purified RPE65 binds all-trans-retinyl palmitate (tRP) with a K(D) = 20 pM [9].
• Lack of effect of RPE65 removal on the enzymatic processing of all-trans-retinol into 11-cis-retinol in vitro [7].

Analytical, diagnostic and therapeutic context of RPE65

• RPE65 cellular localization was determined using immunohistochemistry on flatmounted retinas and retinal sections [8].

References