OPTOREMODE

Retinitis pigmentosa (RP) is a hereditary rare disease of the retina leading to incurable blindness. When most photoreceptors degenerate and lost their ability to respond to light, a substantial quantity of dormant cone photoreceptors can persist. The RP retinal tissue therefore contains these dormant cones and two additional neuronal layers. Reactivation of this residual tissue with retinal prostheses can restore some vision in blind patients. We recently showed that optogenetic reactivation of cone photoreceptors with a photosensitive ionic pump could provide an alternative strategy for a greater visual acuity. However, after the photoreceptor degeneration, the retinal tissue continues to undergo a cellular and molecular remodeling, which needs to be considered to optimize future clinical trials. Our first aim is to characterize this tissue plasticity at the functional and anatomical level using optogenetically reactivated tissue. The second aim is to define whether this retinal remodeling can be stopped when the tissue is optogenetically reactivated. Finally, to improve RP diagnosis, we will develop a mathematical analysis of electroretinogram, the clinical electrophysiological measurement of retinal activity, to uncover nearly extinguished signals. Using optogenetically-modified animals, we will also further assess the cellular significance of electroretinogram measurements. OPTOREMODE will therefore pave the way to clinical trials for optogenetic reactivation of the retina in RP patients and improve their diagnosis.