Analysis of the visual cycle in cellular retinol-binding protein type I (CRBPI) knockout mice

Invest Ophthalmol Vis Sci. 2002 Jun;43(6):1730-5.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acyltransferases / metabolism
  • Animals
  • Cell Cycle / physiology
  • Dark Adaptation
  • Electroretinography
  • Mice
  • Mice, Knockout
  • Photic Stimulation
  • Retina / cytology
  • Retina / metabolism*
  • Retinoids / metabolism*
  • Retinol-Binding Proteins / physiology*
  • Retinol-Binding Proteins, Cellular
  • Rhodopsin / metabolism*
  • Vision, Ocular / physiology*
  • Vitamin A / metabolism

Substances

  • Retinoids
  • Retinol-Binding Proteins
  • Retinol-Binding Proteins, Cellular
  • Vitamin A
  • Rhodopsin
  • Acyltransferases
  • lecithin-retinol acyltransferase