Abstract
Regeneration of the visual chromophore, 11-cis-retinal, is a crucial step in the visual cycle required to sustain vision. This cycle consists of sequential biochemical reactions that occur in photoreceptor cells and the retinal pigmented epithelium (RPE). Oxidation of 11-cis-retinol to 11-cis-retinal is accomplished by a family of enzymes termed 11-cis-retinol dehydrogenases, including RDH5 and RDH11. Double deletion of Rdh5 and Rdh11 does not limit the production of 11-cis-retinal in mice. Here we describe a third retinol dehydrogenase in the RPE, RDH10, which can produce 11-cis-retinal. Mice with a conditional knock-out of Rdh10 in RPE cells (Rdh10 cKO) displayed delayed 11-cis-retinal regeneration and dark adaption after bright light illumination. Retinal function measured by electroretinogram after light exposure was also delayed in Rdh10 cKO mice as compared with controls. Double deletion of Rdh5 and Rdh10 (cDKO) in mice caused elevated 11/13-cis-retinyl ester content also seen in Rdh5(-/-)Rdh11(-/-) mice as compared with Rdh5(-/-) mice. Normal retinal morphology was observed in 6-month-old Rdh10 cKO and cDKO mice, suggesting that loss of Rdh10 in the RPE does not negatively affect the health of the retina. Compensatory expression of other retinol dehydrogenases was observed in both Rdh5(-/-) and Rdh10 cKO mice. These results indicate that RDH10 acts in cooperation with other RDH isoforms to produce the 11-cis-retinal chromophore needed for vision.
Highlights
RDH10 is a candidate 11-cis-retinol dehydrogenase in the retinal pigmented epithelium (RPE) capable of regenerating the visual chromophore, 11-cis-retinal
Retinol Dehydrogenase Activity of RDH10 Expressed in Sf9 Cells—To examine retinol dehydrogenase activity of RDH10, human RDH10 cloned from human primary RPE cells was expressed in Sf9 cells
Apart from Rdh5 and Rdh11, Rdh10 participates in the production of 11-cis-retinal in the RPE
Summary
RDH10 is a candidate 11-cis-retinol dehydrogenase in the retinal pigmented epithelium (RPE) capable of regenerating the visual chromophore, 11-cis-retinal. Regeneration of the visual chromophore, 11-cis-retinal, is a crucial step in the visual cycle required to sustain vision This cycle consists of sequential biochemical reactions that occur in photoreceptor cells and the retinal pigmented epithelium (RPE). Mice with a conditional knock-out of Rdh in RPE cells (Rdh cKO) displayed delayed 11-cis-retinal regeneration and dark adaption after bright light illumination. Compensatory expression of other retinol dehydrogenases was observed in both Rdh5؊/؊ and Rdh cKO mice These results indicate that RDH10 acts in cooperation with other RDH isoforms to produce the 11-cis-retinal chromophore needed for vision. Rdh5Ϫ/Ϫ Rdh11Ϫ/Ϫ mice still produce 11-cis-retinal in the RPE, suggesting that Rdh plays a minor but complementary role in 11-cis-retinal regeneration [12]. Our data provide evidence that Rdh plays a complementary role in regenerating 11-cis-retinal in mice
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