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Drug screening with zebrafish visual behavior identifies carvedilol as a potential treatment for an autosomal dominant form of retinitis pigmentosa

Retinitis Pigmentosa (RP) is a mostly incurable inherited retinal degeneration affecting approximately 1 in 4000 individuals globally. The goal of this work was to identify drugs that can help patients suffering from the disease. To accomplish this, we screened drugs on a zebrafish autosomal dominan...

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Autores principales: Ganzen, Logan, Ko, Mee Jung, Zhang, Mengrui, Xie, Rui, Chen, Yongkai, Zhang, Liyun, James, Rebecca, Mumm, Jeff, van Rijn, Richard M., Zhong, Wenxuan, Pang, Chi Pui, Zhang, Mingzhi, Tsujikawa, Motokazu, Leung, Yuk Fai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169685/
https://www.ncbi.nlm.nih.gov/pubmed/34075074
http://dx.doi.org/10.1038/s41598-021-89482-z
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author Ganzen, Logan
Ko, Mee Jung
Zhang, Mengrui
Xie, Rui
Chen, Yongkai
Zhang, Liyun
James, Rebecca
Mumm, Jeff
van Rijn, Richard M.
Zhong, Wenxuan
Pang, Chi Pui
Zhang, Mingzhi
Tsujikawa, Motokazu
Leung, Yuk Fai
author_facet Ganzen, Logan
Ko, Mee Jung
Zhang, Mengrui
Xie, Rui
Chen, Yongkai
Zhang, Liyun
James, Rebecca
Mumm, Jeff
van Rijn, Richard M.
Zhong, Wenxuan
Pang, Chi Pui
Zhang, Mingzhi
Tsujikawa, Motokazu
Leung, Yuk Fai
author_sort Ganzen, Logan
collection PubMed
description Retinitis Pigmentosa (RP) is a mostly incurable inherited retinal degeneration affecting approximately 1 in 4000 individuals globally. The goal of this work was to identify drugs that can help patients suffering from the disease. To accomplish this, we screened drugs on a zebrafish autosomal dominant RP model. This model expresses a truncated human rhodopsin transgene (Q344X) causing significant rod degeneration by 7 days post-fertilization (dpf). Consequently, the larvae displayed a deficit in visual motor response (VMR) under scotopic condition. The diminished VMR was leveraged to screen an ENZO SCREEN-WELL REDOX library since oxidative stress is postulated to play a role in RP progression. Our screening identified a beta-blocker, carvedilol, that ameliorated the deficient VMR of the RP larvae and increased their rod number. Carvedilol may directly on rods as it affected the adrenergic pathway in the photoreceptor-like human Y79 cell line. Since carvedilol is an FDA-approved drug, our findings suggest that carvedilol can potentially be repurposed to treat autosomal dominant RP patients.
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spelling pubmed-81696852021-06-02 Drug screening with zebrafish visual behavior identifies carvedilol as a potential treatment for an autosomal dominant form of retinitis pigmentosa Ganzen, Logan Ko, Mee Jung Zhang, Mengrui Xie, Rui Chen, Yongkai Zhang, Liyun James, Rebecca Mumm, Jeff van Rijn, Richard M. Zhong, Wenxuan Pang, Chi Pui Zhang, Mingzhi Tsujikawa, Motokazu Leung, Yuk Fai Sci Rep Article Retinitis Pigmentosa (RP) is a mostly incurable inherited retinal degeneration affecting approximately 1 in 4000 individuals globally. The goal of this work was to identify drugs that can help patients suffering from the disease. To accomplish this, we screened drugs on a zebrafish autosomal dominant RP model. This model expresses a truncated human rhodopsin transgene (Q344X) causing significant rod degeneration by 7 days post-fertilization (dpf). Consequently, the larvae displayed a deficit in visual motor response (VMR) under scotopic condition. The diminished VMR was leveraged to screen an ENZO SCREEN-WELL REDOX library since oxidative stress is postulated to play a role in RP progression. Our screening identified a beta-blocker, carvedilol, that ameliorated the deficient VMR of the RP larvae and increased their rod number. Carvedilol may directly on rods as it affected the adrenergic pathway in the photoreceptor-like human Y79 cell line. Since carvedilol is an FDA-approved drug, our findings suggest that carvedilol can potentially be repurposed to treat autosomal dominant RP patients. Nature Publishing Group UK 2021-06-01 /pmc/articles/PMC8169685/ /pubmed/34075074 http://dx.doi.org/10.1038/s41598-021-89482-z Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Ganzen, Logan
Ko, Mee Jung
Zhang, Mengrui
Xie, Rui
Chen, Yongkai
Zhang, Liyun
James, Rebecca
Mumm, Jeff
van Rijn, Richard M.
Zhong, Wenxuan
Pang, Chi Pui
Zhang, Mingzhi
Tsujikawa, Motokazu
Leung, Yuk Fai
Drug screening with zebrafish visual behavior identifies carvedilol as a potential treatment for an autosomal dominant form of retinitis pigmentosa
title Drug screening with zebrafish visual behavior identifies carvedilol as a potential treatment for an autosomal dominant form of retinitis pigmentosa
title_full Drug screening with zebrafish visual behavior identifies carvedilol as a potential treatment for an autosomal dominant form of retinitis pigmentosa
title_fullStr Drug screening with zebrafish visual behavior identifies carvedilol as a potential treatment for an autosomal dominant form of retinitis pigmentosa
title_full_unstemmed Drug screening with zebrafish visual behavior identifies carvedilol as a potential treatment for an autosomal dominant form of retinitis pigmentosa
title_short Drug screening with zebrafish visual behavior identifies carvedilol as a potential treatment for an autosomal dominant form of retinitis pigmentosa
title_sort drug screening with zebrafish visual behavior identifies carvedilol as a potential treatment for an autosomal dominant form of retinitis pigmentosa
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169685/
https://www.ncbi.nlm.nih.gov/pubmed/34075074
http://dx.doi.org/10.1038/s41598-021-89482-z
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