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R. A. Radu, J. Hu, J. H. Peng, N. L. Mata, D. Bok, G. H. Travis; Regulation of the Visual Cycle by the Non-Photoreceptor Opsin, RGR. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2954.
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RGR is a non-photoreceptor opsin present in the retinal pigment epithelium (RPE). Here, we investigated the role of RGR in light-dependent regulation of the visual cycle for rhodopsin regeneration.
Eyecups (retinas plus RPE) were collected from wild-type (WT), rgr -/- knockout, rpe65 -/- knockout, and rgr -/-, rpe65 -/- double-knockout mice exposed to different light conditions. All mice (except rpe65 -/-) carried the normal (L450) allele of rpe65. Eyecup homogenates were extracted with hexane and analyzed for endogenous retinoids by normal-phase liquid chromatography. RPE homogenates were prepared from dark- and light-adapted WT and rgr-/- mice and used in assays for the visual-cycle enzymes: LRAT, ARAT, Rpe65-isomerase, 11-cis-retinol dehydrogenase (11-cis-RDH), and all-trans-retinol dehydrogenase (all-trans-RDH).
Three-month-old rpe65 -/- mice exposed to bright light (500 lux) showed a 35% reduction in all-trans-retinyl esters (all-trans-RE’s) compared to dark-adapted age-matched rpe65 -/- mice. Light-dependent mobilization of all-trans-RE’s was abolished in rgr -/-, rpe65 -/- mice, suggesting a role for RGR in this process. The rate of 11-cis-retinaldehyde (11-cis-RAL) synthesis was about two-fold slower in rgr -/- versus WT mice. Moreover, Rpe65-isomerase catalytic activity was five-fold lower in rgr -/- versus WT mice. Compared to WT, rgr -/- homogenates showed a two-fold increase in the LRAT. Further, the palmitoyl coenzyme A-dependent retinyl-ester synthase, ARAT was strongly stimulated by light in WT mice. This effect was abolished in rgr -/- mice, suggesting that RGR may mediate light-dependent regulation of ARAT. Finally we observed light-dependent modulation of 11-cis-RDH and all-trans-RDH activity, but these effects were similar in WT and rgr -/- mice.
RGR regulates the activities of several enzymes in RPE cells and may modulate the visual cycle in a light-dependent fashion. RGR strongly stimulates ARAT activity in light, consistent with the proposed role for this enzyme under conditions of high all-trans-ROL. RGR also stimulates Rpe65-isomerase activity independently of light. Finally, RGR appears to inhibit LRAT activity in light. This effect may explain why the light-dependent mobilization of all-trans-RE’s in rpe65 -/- mice is abolished in rgr -/-, rpe65 -/- double-knockout mice. The observed light-dependent modulation of 11-cis-RDH and all-trans-RDH activities in RPE cells may be regulated by a non-photoreceptor opsin distinct from RGR, such as peropsin.
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