論文 - 詳細
| RRC ID | 70318 |
|---|---|
| 著者 | 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. |
| タイトル | Drug screening with zebrafish visual behavior identifies carvedilol as a potential treatment for an autosomal dominant form of retinitis pigmentosa. |
| ジャーナル | 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. |
| 巻・号 | 11(1) |
| ページ | 11432 |
| 公開日 | 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.2 |
| リソース情報 | |
| ゼブラフィッシュ | Tg(zfRh1-3.7B:EGFP)kj2 |