Drug screening with zebrafish visual behavior identifies carvedilol as a potential treatment for an autosomal dominant form of retinitis pigmentosa
Abstract 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 autosoma...
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2021
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oai:doaj.org-article:b5731b7fd28248bebf064ea1a30892112021-12-02T18:25:05ZDrug screening with zebrafish visual behavior identifies carvedilol as a potential treatment for an autosomal dominant form of retinitis pigmentosa10.1038/s41598-021-89482-z2045-2322https://doaj.org/article/b5731b7fd28248bebf064ea1a30892112021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89482-zhttps://doaj.org/toc/2045-2322Abstract 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.Logan GanzenMee Jung KoMengrui ZhangRui XieYongkai ChenLiyun ZhangRebecca JamesJeff MummRichard M. van RijnWenxuan ZhongChi Pui PangMingzhi ZhangMotokazu TsujikawaYuk Fai LeungNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021) |
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Medicine R Science Q Logan Ganzen Mee Jung Ko Mengrui Zhang Rui Xie Yongkai Chen Liyun Zhang Rebecca James Jeff Mumm Richard M. van Rijn Wenxuan Zhong Chi Pui Pang Mingzhi Zhang Motokazu Tsujikawa Yuk Fai Leung Drug screening with zebrafish visual behavior identifies carvedilol as a potential treatment for an autosomal dominant form of retinitis pigmentosa |
| description |
Abstract 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. |
| format |
article |
| author |
Logan Ganzen Mee Jung Ko Mengrui Zhang Rui Xie Yongkai Chen Liyun Zhang Rebecca James Jeff Mumm Richard M. van Rijn Wenxuan Zhong Chi Pui Pang Mingzhi Zhang Motokazu Tsujikawa Yuk Fai Leung |
| author_facet |
Logan Ganzen Mee Jung Ko Mengrui Zhang Rui Xie Yongkai Chen Liyun Zhang Rebecca James Jeff Mumm Richard M. van Rijn Wenxuan Zhong Chi Pui Pang Mingzhi Zhang Motokazu Tsujikawa Yuk Fai Leung |
| author_sort |
Logan Ganzen |
| title |
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_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_sort |
drug screening with zebrafish visual behavior identifies carvedilol as a potential treatment for an autosomal dominant form of retinitis pigmentosa |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/b5731b7fd28248bebf064ea1a3089211 |
| work_keys_str_mv |
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