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TD Leveillard, S Mohand-Said, D Hicks, G Lambrou, JA Sahel; Identification of Rod-Dependent Cone Viability Factor 1, a novel gene controling cone viability . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2725.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: We have established that the secondary loss of cones in a murine model of Retinitis Pigmentosa (RP), the rd1 mouse, results from reduction in the expression of soluble factors expressed by rods that are necessary for cone viability. Our goal was to identify these retinal-derived secreted factor(s) that mediate cone survival using a functional approach. Methods: An expression library in pcDNA-3 was constructed from wild-type mouse neural retina. The library was screened using a viability assay based upon cell survival in cone-enriched embryonic chick retinal cultures. The library was transfected by pools of 100 clones into COS-1 cells by calcium phosphate mediated transient transfection. Positive pools were divided first in sub-pools of 10 clones and finally tested as individual clones. Results: Of 2,100 pools of 100 clones each (representing 210,000 clones), 24 pools were identified that on first screening seemed to have cone survival-promoting activity. From these pools, dilution cloning identified a cDNA that encoded a protein (named Rod-dependent Cone Viability Factor-1 (RdCVF1)) that was reproducibly postive in the survival assay. RdCVF1 rescues cones in the chicken cultures as well as cones from of the rd1 mouse explants in vitro to the same extend as wild type retinal cells. Expression of RdCVF1 is restricted to the retina, it is expressed by rods, and its expression is markedly reduced following retinal degeneration. Conclusion: Restoration of RdCVF1 following rod degeneration, or activation of its downstream signalling pathway, may provide a novel strategy for the treatment of RP and/or other retinal degenerations.
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