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Analysis of the Visual Cycle in Cellular Retinol-Binding Protein Type I (CRBPI) Knockout Mice

¹ From the Departments of Ophthalmology and ² Biochemistry and the ³ Howard Hughes Medical Institute, University of Washington, Seattle, Washington; and the ⁴ Institute of Genetics and Molecular and Cellular Biology, Center for National Scientific Research, National Institute of Health and Medical Research, College of France, Louis Pasteur University, Illkirch, France.

PURPOSE. To determine whether the visual cycle is affected in mice without a functional gene for cellular retinol-binding protein type I (CRBPI^-/- mice).

METHODS. Visual-cycle retinoids and rhodopsin levels were analyzed in eyes of dark adapted (DA) CRBPI^-/- and wild-type (wt) mice before and during recovery from a flash. The rate of dark adaptation was analyzed using electroretinography (ERG).

RESULTS. all-trans-Retinyl esters were reduced to approximately 33% of wt levels in DA CRBPI^-/- mice. Recovery from a flash in wt mice produced transient accumulations of all-trans-retinal and all-trans-retinyl ester, as the pulse of retinoid produced by the flash traversed the visual cycle. In CRBPI^-/- mice, all-trans-retinal accumulated transiently, as in wt mice. However, all-trans-retinol also accumulated transiently in the neural retina, and the transient increase in all-trans-retinyl ester of the wt was reduced. Rates of 11-cis-retinal and rhodopsin formation were comparable in wt and CRBPI^-/- mice. Dark adaptation was delayed by a factor of approximately two.

CONCLUSIONS. The accumulation of all-trans-retinol in neural retina, in the absence of CRBPI and the reduced amount of retinyl esters in the RPE suggest that the binding protein participates in a process that drives diffusion of all-trans-retinol from photoreceptor cells to RPE, perhaps by delivering vitamin A to lecithin-retinol acyltransferase (LRAT) for esterification. Because the perturbation occurred upstream of a slow step of the visual cycle, there was no major impairment of the rate of visual pigment regeneration.

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