Abstract
Purpose :
The nucleoredoxin-like 1 gene (NXNL1) encodes by alternative splicing for the trophic factor RdCVF that stimulates aerobic glycolysis in cones by interaction with its cell surface receptor basigin-1 that is linked to the glucose transporter GLUT1. RdCVF accelerates glucose uptake by cones to sustain cone outer segment renewal. RdCVF prevents secondary cone degeneration in recessive and dominant animal models of retinitis pigmentosa. The second product of the NXNL1 gene, the thioredoxin RdCVFL protects the cones against hyperoxia. We evaluated the effect of a combined administration of the two products encoded by the gene on visual acuity of a recessive model of retinitis pigmentosa, the rd10 mouse.
Methods :
An adeno-associated viral vector encoding for both products of the NXNL1 gene: the thioredoxin RdCVFL and the truncated thioredoxin RdCVF was administrated by subretinal injection to the rd10 mouse. The kinetics of the loss of visual acuity was recorded by optokinetic nystagmus testing. Cone density was then measured using e-conome.
Results :
The loss of visual acuity was statistically significantly retarded after injection of AAV-RdCVF-RdCVFL that an AAV vector targets retinal pigmented epithelial cells and cones and very significantly considering the medical objective. Cone density was higher in animals treated with the combination of the two transgenes. Thus, the administration of RdCVF or RdCVFL prevents visual loss in the rd10 mouse using a non cell- and a cell-autonomous mechanism respectively.
Conclusions :
The results demonstrate that this metabolic and redox treatment will likely be successful in preserving central vision in patients suffering of retinitis pigmentosa independently of causative mutations.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.