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High-sensitivity vision restoration via ectopic expression of chimeric rhodopsin in mice

Katada, Y.; Yoshida, K.; Kobayashi, K.; Hideyuki, O.; Kandori, H.; Tsubota, K.; Kurihara, T.

2020-09-18 neuroscience
10.1101/2020.09.17.301523 bioRxiv
Show 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. One Sentence SummaryOptogenetic therapy with Gloeobacter and human chimeric rhodopsin resulted in highly sensitive visual restoration and protection effects.

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