Phototoxicity Avoidance is a Potential Therapeutic Approach for Retinal Dystrophy Caused by EYS Dysfunction

Overview

Journal JCI Insight

Specialties Biomedical Engineering
General Medicine

Date 2024 Apr 22

PMID 38646933

Authors

Yuki Otsuka

Keiko Imamura

Akio Oishi

Kazuhide Asakawa

Takayuki Kondo

Risako Nakai

Mika Suga

Ikuyo Inoue

Yukako Sagara

Kayoko Tsukita

Kaori Teranaka

Yu Nishimura

Akira Watanabe

Kazuhiro Umeyama

Nanako Okushima

Kohnosuke Mitani

Hiroshi Nagashima

Koichi Kawakami

Keiko Muguruma

Akitaka Tsujikawa

Haruhisa Inoue

Affiliations

Soon will be listed here.

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.

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