Reference - Detail
| RRC ID | 79445 |
|---|---|
| Author | Otsuka Y, Imamura K, Oishi A, Asakawa K, Kondo T, Nakai R, Suga M, Inoue I, Sagara Y, Tsukita K, Teranaka K, Nishimura Y, Watanabe A, Umeyama K, Okushima N, Mitani K, Nagashima H, Kawakami K, Muguruma K, Tsujikawa A, Inoue H. |
| Title | Phototoxicity avoidance is a potential therapeutic approach for retinal dystrophy caused by EYS dysfunction. |
| Journal | JCI Insight |
| Abstract |
Inherited retinal dystrophies (IRDs) are progressive diseases leading to vision loss. Mutation in the eyes shut homolog (EYS) gene is one of the most frequent causes of IRD. However, the mechanism of photoreceptor cell degeneration by mutant EYS has not been fully elucidated. Here, we generated retinal organoids from induced pluripotent stem cells (iPSCs) derived from patients with EYS-associated retinal dystrophy (EYS-RD). In photoreceptor cells of RD organoids, both EYS and G protein-coupled receptor kinase 7 (GRK7), one of the proteins handling phototoxicity, were not in the outer segment, where they are physiologically present. Furthermore, photoreceptor cells in RD organoids were vulnerable to light stimuli, and especially to blue light. Mislocalization of GRK7, which was also observed in eys-knockout zebrafish, was reversed by delivering control EYS into photoreceptor cells of RD organoids. These findings suggest that avoiding phototoxicity would be a potential therapeutic approach for EYS-RD. |
| Volume | 9(8) |
| Published | 2024-4-22 |
| DOI | 10.1172/jci.insight.174179 |
| PII | 174179 |
| PMID | 38646933 |
| PMC | PMC11141876 |
| MeSH | Animals Eye Proteins / genetics Eye Proteins / metabolism Humans Induced Pluripotent Stem Cells* / metabolism Light / adverse effects Mutation Organoids* / metabolism Retina / metabolism Retina / pathology Retinal Dystrophies* / genetics Retinal Dystrophies* / metabolism Retinal Dystrophies* / therapy Zebrafish* |
| IF | 6.205 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 82 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | 293T(RCB2202) |
| Zebrafish | Eys1-4 |
| DNA material | pcDNA3.1-Eys-WT (RDB20435) pcDNA3.1-Eys-c8805a (RDB20446) |