October 23, 2020

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

To achieve mammalian rhodopsin-mediated amplification via G protein activation using retinal gene therapy, we incorporated human rhodopsin cytoplasmic loops into Gloeobacter rhodopsin, thereby generating Gloeobacter and human chimeric rhodopsin (GHCR). Photoreception requires amplification by mammalian rhodopsin through G protein activation, which requires a visual cycle. 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.

 bioRxiv Subject Collection: Neuroscience

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