PUBLICATION
Phototoxicity avoidance is a potential therapeutic approach for retinal dystrophy caused by EYS dysfunction
- Authors
- 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.
- ID
- ZDB-PUB-240423-1
- Date
- 2024
- Source
- JCI insight 9(8): (Journal)
- Registered Authors
- Asakawa, Kazuhide, Kawakami, Koichi
- Keywords
- Ophthalmology, Retinopathy, Stem cells
- MeSH Terms
-
- 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*
- PubMed
- 38646933 Full text @ JCI Insight
Citation
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. (2024) Phototoxicity avoidance is a potential therapeutic approach for retinal dystrophy caused by EYS dysfunction. JCI insight. 9(8):.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping