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- Title
Drug screening with zebrafish visual behavior identifies carvedilol as a potential treatment for an autosomal dominant form of retinitis pigmentosa.
- Authors
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
- 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.
- Subjects
CARVEDILOL; RETINITIS pigmentosa; DRUG use testing; TRANSGENE expression; LABORATORY zebrafish
- Publication
Scientific Reports, 2021, Vol 11, Issue 1, p1
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/s41598-021-89482-z