| RRC ID |
70318
|
| Author |
Ganzen L, Ko MJ, Zhang M, Xie R, Chen Y, Zhang L, James R, Mumm J, van Rijn RM, Zhong W, Pang CP, Zhang M, Tsujikawa M, Leung YF.
|
| Title |
Drug screening with zebrafish visual behavior identifies carvedilol as a potential treatment for an autosomal dominant form of retinitis pigmentosa.
|
| Journal |
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.
|
| Volume |
11(1)
|
| Pages |
11432
|
| Published |
2021-6-1
|
| DOI |
10.1038/s41598-021-89482-z
|
| PII |
10.1038/s41598-021-89482-z
|
| PMID |
34075074
|
| PMC |
PMC8169685
|
| MeSH |
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
|
| IF |
3.998
|
| Resource |
| Zebrafish |
Tg(zfRh1-3.7B:EGFP)kj2 |
