{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T03:16:01Z","timestamp":1792811761109,"version":"4.5.0"},"reference-count":42,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T00:00:00Z","timestamp":1741824000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Council of Science and Technology","award":["GTL24021-201"],"award-info":[{"award-number":["GTL24021-201"]}]},{"name":"National Research Council of Science and Technology","award":["RS-2022-KH125938"],"award-info":[{"award-number":["RS-2022-KH125938"]}]},{"DOI":"10.13039\/501100003710","name":"Ministry of Health and Welfare","doi-asserted-by":"publisher","award":["GTL24021-201"],"award-info":[{"award-number":["GTL24021-201"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003710","name":"Ministry of Health and Welfare","doi-asserted-by":"publisher","award":["RS-2022-KH125938"],"award-info":[{"award-number":["RS-2022-KH125938"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Soonchunhyang University","award":["GTL24021-201"],"award-info":[{"award-number":["GTL24021-201"]}]},{"name":"Soonchunhyang University","award":["RS-2022-KH125938"],"award-info":[{"award-number":["RS-2022-KH125938"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The role of the mitogen-activated protein kinase (MAPK) pathway in choroidal neovascularization (CNV) remains unclear. This study investigates the involvement of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 pathways in CNV development, as well as the therapeutic potential of sprouty 2 (SPRY2), an MAPK inhibitor, in a laser-induced mouse model. The expressions of ERK, JNK, and p38 proteins were analyzed using Western blotting and immunostaining. Immunofluorescence imaging revealed increased p-ERK and p-JNK expression in the retina, retinal pigment epithelium (RPE), and choroid up to day 7. Co-immunostaining showed p-ERK colocalized with CD31, CD11b, F4\/80, cytokeratin, and GFAP in the retina, while p-JNK and p-p38 were associated with angiogenesis and inflammation throughout the retina and choroid. Compared to aflibercept, SPRY2 administration significantly inhibited CNV lesions, endothelial proliferation, fibrosis, and apoptosis, while better-preserving RPE integrity. SPRY2-treated mice showed a stronger reduction in CNV-related inflammation, epithelial\u2013mesenchymal transition, and photoreceptor apoptosis. These results highlight the MAPK pathway\u2019s role in CNV pathogenesis, with ERK primarily mediating M\u00fcller cell gliosis and JNK, contributing to angiogenesis and inflammation. SPRY2 effectively suppressed CNV lesions, supporting its potential as a therapeutic target for CNV treatment via MAPK pathway modulation.<\/jats:p>","DOI":"10.3390\/ijms26062585","type":"journal-article","created":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T06:53:00Z","timestamp":1741848780000},"page":"2585","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The Role of the Mitogen-Activated Protein Kinase Pathway in the Development of Laser-Induced Choroidal Neovascularization"],"prefix":"10.3390","volume":"26","author":[{"given":"Sun Young","family":"Jang","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon 14584, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Young","family":"Yang","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Therapy for Retinal Degeneration, Soonchunhyang University Bucheon Hospital, Bucheon 14584, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Hwan","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon 14584, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeji","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Program in Biomedical Science, Soonchunhyang Graduate School, Soonchunhyang University Bucheon Hospital, Bucheon 14584, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumin","family":"An","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Program in Biomedical Science, Soonchunhyang Graduate School, Soonchunhyang University Bucheon Hospital, Bucheon 14584, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wook Hyun","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon 14584, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Whi","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Gachon University, Incheon 21936, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Woo","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon 14584, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Ha","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon 14584, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyo Song","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon 14584, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jungmook","family":"Lyu","sequence":"additional","affiliation":[{"name":"Department of Medical Science, Konyang University, Daejun 32992, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9689-4384","authenticated-orcid":false,"given":"Tae Kwann","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon 14584, Republic of Korea"},{"name":"Laboratory of Molecular Therapy for Retinal Degeneration, Soonchunhyang University Bucheon Hospital, Bucheon 14584, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1016\/S0140-6736(12)60282-7","article-title":"Age-related macular degeneration","volume":"379","author":"Lim","year":"2012","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1056\/NEJM200002173420707","article-title":"Age-related macular degeneration","volume":"342","author":"Fine","year":"2000","journal-title":"N. 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