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

G. Elachouri, I. Lee-Rivera, E. Clérin, M. Argentini, R. Fridlich, F. Blond, V. Ferracane, Y. Yang, W. Raffelsberger, Jun Wan, J. Bennett, J. A. Sahel, Donald J Zack, T. Léveillard

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)22-29
Number of pages8
JournalFree Radical Biology and Medicine
Volume81
DOIs
StatePublished - 2015

Fingerprint

Vertebrate Photoreceptor Cells
Thioredoxins
Cones
Retinal Rod Photoreceptor Cells
Genes
Defense Mechanisms
Light
Retinal Cone Photoreceptor Cells
Phosphorylation
Alternative Splicing
Phenotype
Enzymes
Proteins

Keywords

  • Adeno-associated
  • Ligth damage
  • Photoreceptors
  • RdCVF
  • Retinitis pigmentosa
  • TAU
  • viral vector

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)
  • Medicine(all)

Cite this

Elachouri, G., Lee-Rivera, I., Clérin, E., Argentini, M., Fridlich, R., Blond, F., ... Léveillard, T. (2015). Thioredoxin rod-derived cone viability factor protects against photooxidative retinal damage. Free Radical Biology and Medicine, 81, 22-29. https://doi.org/10.1016/j.freeradbiomed.2015.01.003

Thioredoxin rod-derived cone viability factor protects against photooxidative retinal damage. / Elachouri, G.; Lee-Rivera, I.; Clérin, E.; Argentini, M.; Fridlich, R.; Blond, F.; Ferracane, V.; Yang, Y.; Raffelsberger, W.; Wan, Jun; Bennett, J.; Sahel, J. A.; Zack, Donald J; Léveillard, T.

In: Free Radical Biology and Medicine, Vol. 81, 2015, p. 22-29.

Research output: Contribution to journalArticle

Elachouri, G, Lee-Rivera, I, Clérin, E, Argentini, M, Fridlich, R, Blond, F, Ferracane, V, Yang, Y, Raffelsberger, W, Wan, J, Bennett, J, Sahel, JA, Zack, DJ & Léveillard, T 2015, 'Thioredoxin rod-derived cone viability factor protects against photooxidative retinal damage', Free Radical Biology and Medicine, vol. 81, pp. 22-29. https://doi.org/10.1016/j.freeradbiomed.2015.01.003
Elachouri, G. ; Lee-Rivera, I. ; Clérin, E. ; Argentini, M. ; Fridlich, R. ; Blond, F. ; Ferracane, V. ; Yang, Y. ; Raffelsberger, W. ; Wan, Jun ; Bennett, J. ; Sahel, J. A. ; Zack, Donald J ; Léveillard, T. / Thioredoxin rod-derived cone viability factor protects against photooxidative retinal damage. In: Free Radical Biology and Medicine. 2015 ; Vol. 81. pp. 22-29.
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