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

Yusaku Katada; Kazuho Yoshida; Kenta Kobayashi; Hideyuki Okano; Hideki Kandori; Kazuo Tsubota; Toshihide Kurihara

doi:10.1101/2020.09.17.301523

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

Yusaku Katada, Kazuho Yoshida, Kenta Kobayashi, Hideyuki Okano, Hideki Kandori, Kazuo Tsubota, Toshihide Kurihara

Department of Ophthalmology

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Journal	Unknown Journal
DOIs	https://doi.org/10.1101/2020.09.17.301523
Publication status	Published - 2020 Sep 18

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)
Immunology and Microbiology(all)
Neuroscience(all)
Pharmacology, Toxicology and Pharmaceutics(all)

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title = "High-sensitivity vision restoration via ectopic expression of chimeric rhodopsin in mice",

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.",

author = "Yusaku Katada and Kazuho Yoshida and Kenta Kobayashi and Hideyuki Okano and Hideki Kandori and Kazuo Tsubota and Toshihide Kurihara",

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AU - Kandori, Hideki

AU - Tsubota, Kazuo

AU - Kurihara, Toshihide

N1 - Publisher Copyright: The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

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AB - 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.

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