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ghizlane elachouri, Irene Lee-Rivera, Emmanuelle Clerin, Frederic Blond, Manuela Argentini, Ram Fridlich, Jean Bennett, Donald Zack, Jose Alain Sahel, Thierry D Leveillard; The thioredoxin RdCVFL protects against photo-oxidative retinal damage. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5467.
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© ARVO (1962-2015); The Authors (2016-present)
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.<br />
Nxnl1-/- mice and theirs littermate were first dark adapted 16 h prior to 2,500 lx exposure. 10 days after exposure, the outer nuclear layer measurement was performed while the cell death quantification was performed as kinetics from 6 to 72 hours. RdCVF expression was assessed by RT-PCR and western blotting and TAU phosphorylation by western blotting. We then administered the AAV-RdCVFL and AAV-RdCVF2L to Nxnl1-/- mice. The outer nuclear layer was measured by optical coherence tomography.<br />
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 RdCVFL 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 analysis demonstrates that the Nxnl1 gene is an endogenous defense mechanism against photo-oxidative stress that is likely of great importance for human vision.
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