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Ying Yang, Emmanuelle Clerin, Manuel SIMONUTTI, celine Jaillard, Stephane Fouquet, José-Alain Sahel, Thierry D Leveillard; Cone rescue depends on Rod-derived Cone Viability Factor. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5444.
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© ARVO (1962-2015); The Authors (2016-present)
Transplantation of normal photoreceptors or subretinal injection of Rod-derived Cone Viability Factor (RdCVF) protein to P23H, a domain model of retinitis pigmentosa rats rescue cone photoreceptors and preserve their function (Yang et al. 2009; 2010). Here, we evaluated the role of RdCVF in the protection observed after transplantation of photoreceptors in the eye of the rd1 mouse, a recessive model of retinitis pigmentosa, original used to study rod to cone interactions. RdCVF is an alternative splicing product of the Nucleoredoxin like 1 gene (Nxnl1). The second product is the thioredoxin RdCVFL.
We performed transplantations of photoreceptor layers of 8-day-old Nxnl1-/- mouse (BALB/c) and its positive controls, the C57BL/6 and the Nxnl1+/+ (BALB/c), in the subretinal space of the rd1 mouse (C3H/HeN) 3 weeks of age. Subsequently, we transplanted photoreceptor layers of 8-day-old Nxnl1-/- mouse after their infection with by AAV2.8-GFP, AAV2.8-RdCVF or AAV2.8RdCVF. The rd1 mice were sacrificed at 6 weeks of age, their eyes were enucleated and retinas were dissected to proceed immunolabeling for cone counting.
Transplantation of photoreceptor layers isolated from the wild-type mice, either the C57BL/6 or the Nxnl1+/+ (BALB/c) mice, protects cones of the rd1 mouse from secondary degeneration as shown by an increase of 24.6% or 37.6% cone density, respectively, compared to the contralateral untreated eyes. When photoreceptor layer of Nxnl1-/- mouse was directly transplanted or transduced using AAV vectors: AAV2.8-GFP and AAV2.8-RdCVFL, prior transplantation, into rd1 mouse, no effext was observed. However, the number of cones was increased by 10.9% in the grafted rd1 mice with photoreceptor layer of the Nxnl1-/- mouse infected with AAV2.8-RdCVF.
Cone rescue of the rd1 mouse by transplantation relies, at least partly, on one of the alternative splicing products of the Nxnl1 gene, the trophic factor RdCVF.
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