Rpe65 is necessary for production of 11-cis-vitamin A in the retinal visual cycle

Nat Genet. 1998 Dec;20(4):344-51. doi: 10.1038/3813.

Abstract

Mutation of RPE65 can cause severe blindness from birth or early childhood, and RPE65 protein is associated with retinal pigment epithelium (RPE) vitamin A metabolism. Here, we show that Rpe65-deficient mice exhibit changes in retinal physiology and biochemistry. Outer segment discs of rod photoreceptors in Rpe65-/- mice are disorganized compared with those of Rpe65+/+ and Rpe65+/- mice. Rod function, as measured by electroretinography, is abolished in Rpe65-/- mice, although cone function remains. Rpe65-/- mice lack rhodopsin, but not opsin apoprotein. Furthermore, all-trans-retinyl esters over-accumulate in the RPE of Rpe65-/- mice, whereas 11-cis-retinyl esters are absent. Disruption of the RPE-based metabolism of all-trans-retinyl esters to 11-cis-retinal thus appears to underlie the Rpe65-/- phenotype, although cone pigment regeneration may be dependent on a separate pathway.

Publication types

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

MeSH terms

  • Animals
  • Carrier Proteins
  • Esters
  • Eye Proteins / genetics
  • Eye Proteins / physiology*
  • Mice
  • Mice, Knockout
  • Microscopy, Electron
  • Mutation
  • Phenotype
  • Proteins*
  • Retina / physiology*
  • Retina / ultrastructure
  • Retinal Rod Photoreceptor Cells / metabolism
  • Retinal Rod Photoreceptor Cells / physiology
  • Rhodopsin / metabolism
  • Vision, Ocular / physiology*
  • Vitamin A / biosynthesis*
  • Vitamin A / metabolism
  • cis-trans-Isomerases

Substances

  • Carrier Proteins
  • Esters
  • Eye Proteins
  • Proteins
  • Vitamin A
  • Rhodopsin
  • retinoid isomerohydrolase
  • cis-trans-Isomerases