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GP Moiseyev, P Goletz, AT C Tsin, TM Redmond, RK Crouch, J-X Ma; Continuous Retinyl Ester Accumulation In Rpe65 Knockout Mice . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4559.
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Purpose: RPE65 knockout (Rpe65-/-) mice generate only minimal amounts of 11-cis retinoids and have elevated levels of all-trans retinyl esters in the retinal pigment epithelium (RPE). The aim of this study was to follow the dynamics of retinyl ester accumulation with age in the RPE65-/- RPE and to understand the possible reasons for overaccumulation of the retinyls esters. Methods: Retinyl esters were extracted and analyzed by HPLC. Expression levels of the proteins involved in visual cycle retinoids metabolism were determined by Western blots. Lecithin retinyl acyltransferase (LRAT) , isomerase and retinyl ester hydrolase (REH) activities were measured in the RPE of wild-type (wt) and Rpe65-/- mice. Results: In wt mice, retinyl ester levels increased with age reaching a plateau at 8 weeks of age. In the RPE65-/- mice, all-trans retinyl esters continuously increased during the entire age analyzed reaching a level over 20-fold higher than in the wt animals at 9 mo. The composition of retinyl esters is similar in wt and Rpe65-/ mice. Wt and RPE65-/- mice have similar LRAT and 11-cis REH activities whereas all-trans REH activity was shown to be reduced by 4-fold in RPE65-/- mice. Conclusion: We conclude that the lack of balance between esterification and hydrolysis may contribute, at least partially, to the continuous accumulation of the all-trans retinyl esters in the RPE of RPE65-/- mice. Supported by NIH EY12231 and EY0439 and RPB.
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