Thioredoxin rod-derived cone viability factor protects against photooxidative retinal damage

Free Radic Biol Med. 2015 Apr;81:22-9. doi: 10.1016/j.freeradbiomed.2015.01.003. Epub 2015 Jan 14.


Rod-derived cone viability factor (RdCVF) is a trophic factor of the thioredoxins family that promotes the survival of cone photoreceptors. It is encoded by the nucleoredoxin-like gene 1 Nxnl1 which also encodes by alternative splicing a long form of RdCVF (RdCVFL), a thioredoxin enzyme that interacts with TAU. The known role of thioredoxins in the defense mechanism against oxidative damage led us to examine the retinal phenotype of the Nxnl1(-/-) mice exposed to photooxidative stress. Here we found that, in contrast to wild-type mice, the rod photoreceptors of Nxnl1(-/-) mice are more sensitive to light after exposure to 1700 or 2500 lx. The delivery of RdCVF by AAV to mice deficient of Nxnl1(-/-) protects rod photoreceptors from light damage. Interestingly, the RdCVF2L protein, encoded by the paralog gene Nxnl2, is able to reduce TAU phosphorylation, as does RdCVFL, but does not protect the rod from light damage. Our result shows that the Nxnl1 gene, through the thioredoxin RdCVFL, is part of an endogenous defense mechanism against photooxidative stress that is likely of great importance for human vision.

Keywords: Adeno-associated viral vector; Ligth damage; Photoreceptors; RdCVF; Retinitis pigmentosa; TAU.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Animals
  • Cell Survival
  • Dependovirus / genetics
  • Eye Proteins / genetics*
  • Eye Proteins / metabolism
  • Female
  • Gene Deletion
  • Gene Transfer Techniques
  • Genetic Therapy / methods*
  • Light / adverse effects
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Oxidation-Reduction
  • Oxidative Stress
  • Phosphorylation
  • Retinal Cone Photoreceptor Cells / metabolism*
  • Retinal Cone Photoreceptor Cells / pathology
  • Retinal Rod Photoreceptor Cells / metabolism*
  • Retinal Rod Photoreceptor Cells / pathology
  • Retinitis Pigmentosa / etiology
  • Retinitis Pigmentosa / genetics
  • Retinitis Pigmentosa / pathology
  • Retinitis Pigmentosa / therapy*
  • Signal Transduction
  • Thioredoxins / genetics*
  • Thioredoxins / metabolism
  • tau Proteins / genetics
  • tau Proteins / metabolism


  • Eye Proteins
  • Mapt protein, mouse
  • RdCVF protein, mouse
  • RdCVF-2 protein, mouse
  • tau Proteins
  • Thioredoxins