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

doi:10.1016/j.isci.2023.107716

Highly sensitive visual restoration and protection via ectopic expression of chimeric rhodopsin in mice

iScience. 2023 Aug 25;26(10):107716. doi: 10.1016/j.isci.2023.107716. eCollection 2023 Oct 20.

Authors

Yusaku Katada^{1

2}, Kazuho Yoshida³, Naho Serizawa^{1

2

4}, Deokho Lee^{1

2}, Kenta Kobayashi⁵, Kazuno Negishi², Hideyuki Okano⁶, Hideki Kandori³, Kazuo Tsubota⁷, Toshihide Kurihara^{1

2}

Affiliations

¹ Laboratory of Photobiology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
² Department of Ophthalmology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
³ Department of Life Science and Applied Chemistry, Nagoya Institute of Technology, Nagoya, Aichi 466-0061, Japan.
⁴ Department of Nutritional Sciences, Toyo University, Kita-ku, Tokyo 115-8650, Japan.
⁵ Section of Viral Vector Development, Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Aichi 444-8585, Japan.
⁶ Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
⁷ Tsubota Laboratory, Inc., Shinjuku-ku, Tokyo 160-0016, Japan.

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.

Keywords: Behavioral neuroscience; Molecular neuroscience; Neurology.