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- Title
Intravitreal Administration of Retinal Organoids-Derived Exosomes Alleviates Photoreceptor Degeneration in Royal College of Surgeons Rats by Targeting the Mitogen-Activated Protein Kinase Pathway.
- Authors
Han, Jung Woo; Chang, Hun Soo; Yang, Jin Young; Choi, Han Sol; Park, Hyo Song; Jun, Hyoung Oh; Choi, Ji Hye; Paik, Sun-Sook; Chung, Kyung Hwun; Shin, Hee Jeong; Nam, Seungyeon; Son, Ji-Hye; Lee, Si Hyung; Lee, Eun Jung; Seo, Kyoung Yul; Lyu, Jungmook; Kim, Jin Woo; Kim, In-Beom; Park, Tae Kwann
- Abstract
Increasing evidence suggests that exosomes are involved in retinal cell degeneration, including their insufficient release; hence, they have become important indicators of retinopathies. The exosomal microRNA (miRNA), in particular, play important roles in regulating ocular and retinal cell functions, including photoreceptor maturation, maintenance, and visual function. Here, we generated retinal organoids (ROs) from human induced pluripotent stem cells that differentiated in a conditioned medium for 60 days, after which exosomes were extracted from ROs (Exo-ROs). Subsequently, we intravitreally injected the Exo-RO solution into the eyes of the Royal College of Surgeons (RCS) rats. Intravitreal Exo-RO administration reduced photoreceptor apoptosis, prevented outer nuclear layer thinning, and preserved visual function in RCS rats. RNA sequencing and miRNA profiling showed that exosomal miRNAs are mainly involved in the mitogen-activated protein kinase (MAPK) signaling pathway. In addition, the expression of MAPK-related genes and proteins was significantly decreased in the Exo-RO-treated group. These results suggest that Exo-ROs may be a potentially novel strategy for delaying retinal degeneration by targeting the MAPK signaling pathway.
- Subjects
ROYAL College of Surgeons of England; MITOGEN-activated protein kinases; INDUCED pluripotent stem cells; EXOSOMES; PHOTORECEPTORS; CELL physiology
- Publication
International Journal of Molecular Sciences, 2023, Vol 24, Issue 15, p12068
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms241512068