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

Logan Ganzen, MeeJung Ko, Mengrui Zhang, Rui Xie, Yongkai Chen, Liyun Zhang, Rebecca James, Jeff Mumm, Richard van Rijn, Wenxuan Zhong, Chi Pui Pang, Mingzhi Zhang, Motokazu Tsujikawa, Yuk Fai Leung

Abstract: h3>Abstract</h3> <p>Retinitis 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 <i>rhodopsin</i> transgene (<i>Tg(rho:Hsa</i>.<i>RH1_Q344X</i>)) 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.</p><h3>Summary Statement</h3> <p>This 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.</p>

External IDs:doi:10.1101/2020.07.28.225789