{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T09:09:26Z","timestamp":1790932166493,"version":"4.1.0"},"reference-count":94,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:00:00Z","timestamp":1758240000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education, Science, and Technology (MEST)","award":["NRF-2022R1F1A1073895"],"award-info":[{"award-number":["NRF-2022R1F1A1073895"]}]},{"name":"Ministry of Education, Science, and Technology (MEST)","award":["2025IL0022"],"award-info":[{"award-number":["2025IL0022"]}]},{"name":"Asan Institute for Life Sciences, Seoul, Republic of Korea","award":["NRF-2022R1F1A1073895"],"award-info":[{"award-number":["NRF-2022R1F1A1073895"]}]},{"name":"Asan Institute for Life Sciences, Seoul, Republic of Korea","award":["2025IL0022"],"award-info":[{"award-number":["2025IL0022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Alkali burns to the cornea cause severe damage characterized by an intense inflammatory response driven by inflammatory cytokines, which orchestrate pathological processes, including neovascularization, fibrosis, apoptosis, abnormal cell proliferation, and disorganization of the extracellular matrix (ECM), often resulting in permanent vision impairment or loss. Rapamycin (RAPA), a well-known mTOR inhibitor with potent immunosuppressive activity and pleiotropic therapeutic effects, was investigated as a novel restorative modality for promoting corneal wound healing in a mouse model of alkali burn injury. Topical RAPA treatment significantly reduced clinical signs of inflammation and decreased the infiltration of F4\/80+ macrophages and CD45+ leukocytes, along with suppressed expression of pro-inflammatory cytokines (TNF-\u03b1, IL-1\u03b2, IL-6, and IL-17A). RAPA also markedly downregulated angiogenic mediators, such as VEGF, and endothelial markers, like CD31, resulting in significant inhibition of neovascularization. Furthermore, it prevented fibrotic tissue formation and myofibroblast activation, as evidenced by reduced \u03b1-SMA levels, and attenuated pathological matrix remodeling through decreased MMP-9 expression. Notably, RAPA preserved epithelial barrier function by maintaining the tight junction protein ZO-1 and reduced both apoptotic cell death (TUNEL) and dysregulated proliferation (Ki67+), thereby preserving the functional and structural integrity of the cornea. In conclusion, RAPA represents a promising therapeutic candidate for managing severe corneal alkali burn injuries, with the potential to enhance corneal wound healing, minimize long-term complications, and protect visual function.<\/jats:p>","DOI":"10.3390\/bioengineering12090998","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T12:33:32Z","timestamp":1758285212000},"page":"998","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Rapamycin Mitigates Corneal Damage in a Mouse Model of Alkali Burn Injury"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0503-8900","authenticated-orcid":false,"given":"Basanta","family":"Bhujel","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Asan Medical Center, College of Medicine, University of Ulsan, Seoul 05505, Republic of Korea"},{"name":"Department of Medical Science, Graduate School, University of Ulsan, Seoul 05505, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woojune","family":"Hur","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Asan Medical Center, College of Medicine, University of Ulsan, Seoul 05505, Republic of Korea"},{"name":"Department of Medical Science, Graduate School, University of Ulsan, Seoul 05505, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seorin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Asan Medical Center, College of Medicine, University of Ulsan, Seoul 05505, Republic of Korea"},{"name":"Department of Medical Science, Graduate School, University of Ulsan, Seoul 05505, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Asan Medical Center, College of Medicine, University of Ulsan, Seoul 05505, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho Seok","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Asan Medical Center, College of Medicine, University of Ulsan, Seoul 05505, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8571-8350","authenticated-orcid":false,"given":"Jae Yong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Asan Medical Center, College of Medicine, University of Ulsan, Seoul 05505, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1167\/iovs.61.12.20","article-title":"Wound healing after alkali burn injury of the cornea involves Nox4-type NADPH oxidase","volume":"61","author":"Hakami","year":"2020","journal-title":"Invest. 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