PUBLICATION

Drug screening with zebrafish visual behavior identifies carvedilol as a potential treatment for an autosomal dominant form of retinitis pigmentosa

Authors
Ganzen, L., Ko, M.J., Zhang, M., Xie, R., Chen, Y., Zhang, L., James, R., Mumm, J., van Rijn, R.M., Zhong, W., Pang, C.P., Zhang, M., Tsujikawa, M., Leung, Y.F.
ID
ZDB-PUB-210603-44
Date
2021
Source
Scientific Reports   11: 11432 (Journal)
Registered Authors
Leung, Yuk Fai, Mumm, Jeff, Tsujikawa, Motokazu
Keywords
none
MeSH Terms
  • Animals
  • Animals, Genetically Modified*/genetics
  • Animals, Genetically Modified*/metabolism
  • Behavior, Animal/drug effects*
  • Cell Line
  • Drug Evaluation, Preclinical
  • Genetic Diseases, Inborn*/drug therapy
  • Genetic Diseases, Inborn*/genetics
  • Genetic Diseases, Inborn*/metabolism
  • Humans
  • Mutation
  • Retinal Rod Photoreceptor Cells
  • Retinitis Pigmentosa*/drug therapy
  • Retinitis Pigmentosa*/genetics
  • Retinitis Pigmentosa*/metabolism
  • Rhodopsin*/genetics
  • Rhodopsin*/metabolism
  • Transgenes
  • Vision, Ocular*/drug effects
  • Vision, Ocular*/immunology
  • Zebrafish*/genetics
  • Zebrafish*/metabolism
PubMed
34075074 Full text @ Sci. Rep.
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes