Drug Screening with Zebrafish Visual Behavior Identifies Carvedilol as a Potential Treatment for Retinitis Pigmentosa

Abstract

AbstractRetinitis Pigmentosa (RP) is an incurable inherited retinal degeneration affecting approximately 1 in 4,000 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 RP model. This model expresses a truncated human rhodopsin transgene (Tg(rho:Hsa.RH1_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 can act directly on rods as it affected the adrenergic pathway in a rod-like human Y79 cell line. Since carvedilol is an FDA-approved drug, our findings suggest that carvedilol can potentially be repurposed to treat RP patients.Summary StatementThis paper presents the utilization of zebrafish visual behavior, a novel paradigm to screen and identify drugs to treat retinitis pigmentosa, an incurable retinal-degenerative disease.