Intravitreal Administration of Retinal Organoids-Derived Exosomes Alleviates Photoreceptor Degeneration in Royal College of Surgeons Rats by Targeting the Mitogen-Activated Protein Kinase Pathway
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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.
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The miRNAs in the tandem construct were arranged as hsa-miR-122-5p, hsa-let-7a-5p, and hsa-miR-26a-5p based on normalized expression levels from miRNA profiling of retinal organoid secretion.
“The miRNAs were arranged sequentially as hsa-miR-122-5p, hsa-let-7a-5p, and hsa-miR-26a-5p, based on normalized expression levels obtained from miRNA profiling of retinal organoid secretion 26 , reflecting a physiologically relevant expression pattern in the retina.”
From rAAV-mediated Multi-miRNA Delivery Targeting MAPK Pathway Suppresses Laser-induced Choroidal Neovascularization in Mice (2026) · cites this paper as [26]
Results §2.4 reports miRNA profiling of retinal-organoid-derived exosomes, and Methods §4.15 describes normalization of miRNA expression levels; page numbers are unavailable. The copy does not establish the stated order of hsa-miR-122-5p, hsa-let-7a-5p, and hsa-miR-26a-5p or link that order to their normalized expression levels, so it supports the profiling basis but not the specific arrangement. (LLM, conf=0.82)
Experimental — accuracy not yet measuredExosomal miRNAs derived from retinal organoids can target the MAPK signaling pathway and alleviate photoreceptor cell death in RCS rats.
“Furthermore, we showed that exosomal miRNAs derived from retinal organoids can target the MAPK signaling pathway and alleviate photoreceptor cell death in RCS rats 26 .”
From rAAV-mediated Multi-miRNA Delivery Targeting MAPK Pathway Suppresses Laser-induced Choroidal Neovascularization in Mice (2026) · cites this paper as [26]
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AAV2.7m8-Mediated MicroRNA Expression Suppresses VEGF-Induced Angiogenic Responses in HUVEC
Yang, J. Y., Choi, J.-S., & Park, T. K. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27073123 · Cited by 1 · see citing works
Self-citationThe synergistic applications of organoids and exosomes in disease modeling and disease treatment
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Opportunities and challenges in studying non-coding RNAs using neural organoid models
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- Authors
- Han, J., Chang, H., Yang, J., Choi, H., Park, H., Jun, H., Choi, J., Paik, S.-S., Chung, K., Shin, H., Nam, S., Son, J.-H., Lee, S., Lee, E., Seo, K., Lyu, J., Kim, J., Kim, I.-B., & Park, T.
- Affiliations
- Soonchunhyang University Hospital Bucheon (KR)
- Soonchunhyang University (KR)
- Catholic University of Korea (KR)
- University of Notre Dame (US)
- Korea Advanced Institute of Science and Technology (KR)
- Yonsei University (KR)
- Konyang University (KR)
- Corresponding author
- Park, Tae
- ORCID
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2023-07-27
- Volume
- 24
- Issue
- 15
- Pages
- 12068
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC10419150
- OpenAlex
- W4385346716
- Cited by
- 20
- References
- 75
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 7
- FWCI
- 1.78
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Technology Innovation Program (20009844, HI21C0317)
- Ministry of Health & Welfare, Republic of Korea (20009844, HI21C0317)
- Ministry of Trade, Industry, and Energy (MI, Korea) (20009844, HI21C0317)
- Soonchunhyang University research fund (20009844, HI21C0317)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Keywords
- retinal organoids, exosomes, intravitreal injection, photoreceptor degeneration, retinal degeneration, mitogen-activated protein kinase signaling pathway, exosomal microRNAs, photoreceptor apoptosis, outer nuclear layer, visual function, induced pluripotent stem cells, exosome therapy
- MeSH terms
- Animals, Humans, Retinal Degeneration, Reactive Oxygen Species, Mitogen-Activated Protein Kinases, MicroRNAs, Rats, Exosomes, Induced Pluripotent Stem Cells, Surgeons
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