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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.more » « less
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Venkatraman, Prahatha; Mills-Henry, Ishara; Padmanabhan, Karthik Ramaswamy; Pascuzzi, Pete; Hassan, Menna; Zhang, Jingyi; Zhang, Xinlian; Ma, Ping; Pang, Chi Pui; Dowling, John E.; et al (, Investigative Opthalmology & Visual Science)null (Ed.)
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Xie, Rui; Zhang, Mengrui; Venkatraman, Prahatha; Zhang, Xinlian; Zhang, Gaonan; Carmer, Robert; Kantola, Skylar A.; Pang, Chi Pui; Ma, Ping; Zhang, Mingzhi; et al (, PLOS ONE)Neuhauss, Stephan C.F. (Ed.)
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