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

G Elachouri (1) , I Lee-Rivera (1) , E Clérin (1) , M Argentini (1) , R Fridlich (1) , F Blond (1) , V Ferracane (1) , Yingying Yang (2) , W Raffelsberger (3) , Jun Wan (4) , J Bennett (5) , José-Alain Sahel (1) , D J Zack (1) , T Léveillard (1)

1 Institut de la Vision
2 School of Mechanical Engineering and Automation
3 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire
4 Departments of Ophtalmology, molecular biology and genetics, neuroscience and Institute of genetic medicine
5 Scheie Eye Institute

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 photo-oxidative 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 1,700 or 2,500 lx. The delivery of RdCVF by AAV to mice deficient of Nxnl1-/- protects rods 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 photo-oxidative stress that is likely of great importance for human vision.

Mots clés: TAU; RdCVF; Photoreceptors; Adeno-associated viral vector; Ligth damage; Retinitis pigmentosa

Domaines: Génétique; Organes des sens

G Elachouri, I Lee-Rivera, E Clérin, M Argentini, R Fridlich, et al.. Thioredoxin rod-derived cone viability factor protects against photooxidative retinal damage. Advances in Free Radical Biology & Medicine, 2015, 81, pp.22-29. ⟨10.1016/j.freeradbiomed.2015.01.003⟩. ⟨hal-01110160⟩