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N.M. Qtaishat, G.H. Travis, D.R. Pepperberg; Post–Bleach Kinetics of Retinoid Cycling in abcr–/– Mice . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1060.
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Purpose: Rhodopsin regeneration after bleaching illumination involves the cycling of retinoid in the retina–RPE system. ABCR protein is thought to act in this process by moving all–trans retinal (as N–retinylidene–phosphatidylethanolamine) from the disk lumen to the rod cytosol. Mutations in the gene encoding ABCR have been linked to Stargardt disease and other retinal degenerations. We have investigated bleach–induced retinoid processing in abcr knockout mice (abcr–/–), which lack ABCR, and compared the results obtained with those of similar experiments previously performed on wildtype mice (age: 2 months) (ref. 1). Methods: Dark–adapted abcr–/– mice (age: approx. 6 wks) were anesthetized with ketamine/xylazine. Following pupil dilation, one eye received a 2–min bleach (green light); the fellow eye was shielded from light and served as a control. Mice were maintained in darkness for 0, 30, 90, 180 or 300 min, and then sacrificed. Retinas and RPEs were analyzed for molar amounts of 11–cis, all–trans and 13–cis retinal, all–trans retinol and retinyl ester by extraction and HPLC (1). Results: In the unilluminated (dark–adapted) 6–wk abcr–/– eye, the molar amount of both 11–cis retinal in the retina (avearge: 140 pmol) and of total retinoid in the retina–plus–RPE (average: 190 pmol) represented ∼50% of the corresponding amounts in the 2–month wildtype eye. Bleach–induced retinoid kinetics in abcr–/– and wildtype mice were similar in several respects. In both groups, the bleach produced an immediate drop of ∼45% in 11–cis retinal within the retina. It also produced an immediate ∼6–fold increase in all–trans retinal, and a subsequent substantial drop toward baseline within 30 min. Also in both groups, little if any all–trans retinol appeared at any post–bleach time, and a peak amount of retinyl ester appeard at ∼90 min post–bleach. However, in abcr–/–'s, full recovery of 11–cis retinal to pre–bleach baseline was evident at 180 min; in wildtypes this required ∼300 min. Conclusions: The data indicate a general similarity of bleach–induced retinoid kinetics in abcr–/– and wildtype mice under the present experimental conditions, a finding that places constraints on the effects of ABCR deficiency at early ages (6 wks). The apparent, somewhat faster recovery of 11–cis retinal in the abcr–/– could be a consequence of the relatively lower total amount of retinoid in the 6–wk abcr–/– eye. Alternatively, the difference could reflect a perturbing action of ABCR deficiency on retinoid cycle operation even at 6 wks of age. (1) Qtaishat et al. (1999) IOVS 40:1040–1049.
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