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Drug screening with zebrafish visual behavior identifies carvedilol as a potential treatment for an autosomal dominant form of retinitis pigmentosa
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Drug screening with zebrafish visual behavior identifies carvedilol as a potential treatment for an autosomal dominant form of retinitis pigmentosa
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Drug screening with zebrafish visual behavior identifies carvedilol as a potential treatment for an autosomal dominant form of retinitis pigmentosa
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Journal Article
Drug screening with zebrafish visual behavior identifies carvedilol as a potential treatment for an autosomal dominant form of retinitis pigmentosa
2021
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 631/378
/ Animals
/ Animals, Genetically Modified - genetics
/ Animals, Genetically Modified - metabolism
/ Behavior, Animal - drug effects
/ Drug Evaluation, Preclinical
/ Drugs
/ Genetic Diseases, Inborn - drug therapy
/ Genetic Diseases, Inborn - genetics
/ Genetic Diseases, Inborn - metabolism
/ Humanities and Social Sciences
/ Humans
/ Larvae
/ Medicine
/ Mutation
/ Retina
/ Retinal Rod Photoreceptor Cells
/ Retinitis Pigmentosa - drug therapy
/ Retinitis Pigmentosa - genetics
/ Retinitis Pigmentosa - metabolism
/ Science
