Highly sensitive visual restoration and protection via ectopic expression of chimeric rhodopsin in mice
Yusaku Katada, Kazuho Yoshida, Naho Serizawa, Deokho Lee, Kenta Kobayashi, Kazuno Negishi, Hideyuki Okano, Hideki Kandori, Kazuo Tsubota, Toshihide Kurihara
Abstract
Photoreception requires amplification by mammalian rhodopsin through G protein activation, which requires a visual cycle. To achieve this in retinal gene therapy, we incorporated human rhodopsin cytoplasmic loops into Gloeobacter rhodopsin, thereby generating Gloeobacter and human chimeric rhodopsin (GHCR). In a murine model of inherited retinal degeneration, we induced retinal GHCR expression by intravitreal injection of a recombinant adeno-associated virus vector. Retinal explant and visual thalamus electrophysiological recordings, behavioral tests, and histological analysis showed that GHCR restored dim-environment vision and prevented the progression of retinal degeneration. Thus, GHCR may be a potent clinical tool for the treatment of retinal disorders.