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C. Jaillard, I. Lee-rivera, F. Chalmel, O. Poch, B. Kinzel, J. Sahel, T. Leveillard; Rod-Derived Cone Viability Factor-2 : A Novel Bifunctional-Thioredoxin-Like Protein Required for Maintenance of Retinal Photoreceptors. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2992.
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© ARVO (1962-2015); The Authors (2016-present)
Cone degeneration is the hallmark of the inherited retinal disease retinitis pigmentosa. We have previously identified a trophic factor "Rod-derived ConeViability Factor (RdCVF) that is secreted by rods and promote cone viability in mouse model of the disease.
We used a bioinformatic approach to identify , a second trophic factor belonging to the Rod-derived Cone Viability Factor family, RdCVF2.We analysed the phenotype of RdCVF2 knockout mice. The visual function of the RdCVF2 -/- mice has been tested by electroretinography. Next, we tested for possible cone loss in the RdCVF2 -/- mice at two and ten months of age. The animals were sacrificed and the retinas of RdCVF2 -/- mice and their isogenic controls were dissected and labelled with peanut hemaglutinin (PNA) a lectin binding specifically to the matrix sheet surrounding cones. PNA was revealed using an anti-PNA coupled to rhodamine The retinas were flat-mounted and processed for automated image acquisition and cell counting on our platform.
We report the bioinformatic identification and the experimental analysis of RdCVF2, a second trophic factor belonging to the Rod-derived Cone Viability Factor family. The mouse RdCVF gene is known to be bifunctional, encoding both a long thioredoxin-like isoform (RdCVF-L) and a short isoform with trophic cone photoreceptor viability activity (RdCVF-S). RdCVF2 shares many similarities with RdCVF in terms of gene structure, expression in a rod-dependent manner. Furthermore, like RdCVF, the RdCVF2 short isoform exhibits cone rescue activity.Next, we Characterized RdCVF2-/- phenotype. The postnatal development of retinal photoreceptors in the RdCVF2-/- mice was indistinguishable from that of wildt type controls as judged by histology and electroretinograms (ERGs) in younger mice. By 10 months of age, 30% of cones were lost. Along with the loss of cones, ERG amplitudes declined so that by 10 months the a- and b-waves were reduced by >60% compared with those of age-matched wild type controls.
Taken together, these findings define a new family of bifunctional genes which are expressed in vertebrate retina, encode trophic cone viability factors, and have major therapeutic potential for human retinal neurodegenerative diseases such as retinitis pigmentosa.
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