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

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...

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Autores principales: Katada, Yusaku, Yoshida, Kazuho, Serizawa, Naho, Lee, Deokho, Kobayashi, Kenta, Negishi, Kazuno, Okano, Hideyuki, Kandori, Hideki, Tsubota, Kazuo, Kurihara, Toshihide
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10504486/
https://www.ncbi.nlm.nih.gov/pubmed/37720108
http://dx.doi.org/10.1016/j.isci.2023.107716
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author Katada, Yusaku
Yoshida, Kazuho
Serizawa, Naho
Lee, Deokho
Kobayashi, Kenta
Negishi, Kazuno
Okano, Hideyuki
Kandori, Hideki
Tsubota, Kazuo
Kurihara, Toshihide
author_facet Katada, Yusaku
Yoshida, Kazuho
Serizawa, Naho
Lee, Deokho
Kobayashi, Kenta
Negishi, Kazuno
Okano, Hideyuki
Kandori, Hideki
Tsubota, Kazuo
Kurihara, Toshihide
author_sort Katada, Yusaku
collection PubMed
description 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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spelling pubmed-105044862023-09-17 Highly sensitive visual restoration and protection via ectopic expression of chimeric rhodopsin in mice Katada, Yusaku Yoshida, Kazuho Serizawa, Naho Lee, Deokho Kobayashi, Kenta Negishi, Kazuno Okano, Hideyuki Kandori, Hideki Tsubota, Kazuo Kurihara, Toshihide iScience Article 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. Elsevier 2023-08-25 /pmc/articles/PMC10504486/ /pubmed/37720108 http://dx.doi.org/10.1016/j.isci.2023.107716 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Katada, Yusaku
Yoshida, Kazuho
Serizawa, Naho
Lee, Deokho
Kobayashi, Kenta
Negishi, Kazuno
Okano, Hideyuki
Kandori, Hideki
Tsubota, Kazuo
Kurihara, Toshihide
Highly sensitive visual restoration and protection via ectopic expression of chimeric rhodopsin in mice
title Highly sensitive visual restoration and protection via ectopic expression of chimeric rhodopsin in mice
title_full Highly sensitive visual restoration and protection via ectopic expression of chimeric rhodopsin in mice
title_fullStr Highly sensitive visual restoration and protection via ectopic expression of chimeric rhodopsin in mice
title_full_unstemmed Highly sensitive visual restoration and protection via ectopic expression of chimeric rhodopsin in mice
title_short Highly sensitive visual restoration and protection via ectopic expression of chimeric rhodopsin in mice
title_sort highly sensitive visual restoration and protection via ectopic expression of chimeric rhodopsin in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10504486/
https://www.ncbi.nlm.nih.gov/pubmed/37720108
http://dx.doi.org/10.1016/j.isci.2023.107716
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