The interplay of environmental luminance and genetics in the retinal dystrophy induced by the dominant RPE65 mutation

Proc Natl Acad Sci U S A. 2022 Mar 15;119(11):e2115202119. doi: 10.1073/pnas.2115202119. Epub 2022 Mar 10.


SignificanceIn humans, genetic mutations in the retinal pigment epithelium (RPE) 65 are associated with blinding diseases, for which there is no effective therapy alleviating progressive retinal degeneration in affected patients. Our findings uncovered that the increased free opsin caused by enhancing the ambient light intensity increased retinal activation, and when compounded with the RPE visual cycle dysfunction caused by the heterozygous D477G mutation and aggregation, led to the onset of retinal degeneration.

Keywords: RPE65; photoreceptor; retinal degeneration; visual cycle.

MeSH terms

  • Animals
  • Eye Proteins* / genetics
  • Genes, Dominant*
  • Mice
  • Mice, Knockout
  • Mutation
  • Retina / enzymology
  • Retina / pathology
  • Retinal Dystrophies* / genetics
  • Vision, Ocular
  • cis-trans-Isomerases* / genetics


  • Eye Proteins
  • retinoid isomerohydrolase
  • cis-trans-Isomerases