{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T05:14:06Z","timestamp":1763788446633,"version":"3.45.0"},"reference-count":31,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2021R1A2C2093617"],"award-info":[{"award-number":["NRF-2021R1A2C2093617"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"2021 Cheil-Nammyung Foundation Research Fund.","award":["2021 Cheil-Nammyung Foundation Research Fund."],"award-info":[{"award-number":["2021 Cheil-Nammyung Foundation Research Fund."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>This study investigated the region-specific roles of transforming growth factor-\u03b22 (TGF-\u03b22) and angiotensin II (AngII) in extracellular matrix (ECM) remodeling and inflammatory responses within scleral tissues surrounding the optic nerve head (ONH), using primary human fibroblasts from posterior sclera, peripapillary sclera (ppScl), and fibroblast-like cells from lamina cribrosa (LC). In vivo validation was performed in a chronic ocular hypertension rat model. Fibrotic and inflammatory markers were analyzed by Western blotting, quantitative PCR, and immunocytochemistry following TGF-\u03b22 or AngII stimulation, and in vivo effects were assessed after subtenon injection of pathway-specific inhibitors. TGF-\u03b22 induced robust upregulation of \u03b1-smooth muscle actin, collagen type I, and fibronectin across all scleral regions, whereas AngII elicited regionally confined pro-inflammatory responses, particularly in the LC and ppScl, characterized by increased cyclooxygenase-2 expression. Inhibition of either pathway reduced ECM deposition in vivo, but only AngII blockade significantly attenuated glial activation and preserved retinal ganglion cells. These findings demonstrate that TGF-\u03b22 predominantly drives fibrosis, while AngII promotes region-specific neuroinflammation, and that inflammation, rather than fibrosis alone, plays a critical role in glaucomatous neurodegeneration. Targeting both fibrotic and inflammatory mechanisms in a region-specific manner may offer improved neuroprotection in glaucoma.<\/jats:p>","DOI":"10.3390\/cells14221830","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T13:25:27Z","timestamp":1763645127000},"page":"1830","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Region-Specific Roles of TGF-\u03b22 and Angiotensin II in Fibrotic and Inflammatory Remodeling of the Optic Nerve Head"],"prefix":"10.3390","volume":"14","author":[{"given":"Si-Eun","family":"Oh","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Bucheon St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Bucheon 14647, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie-Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Se-Eun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Bucheon St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Bucheon 14647, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chan-Kee","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4536-5332","authenticated-orcid":false,"given":"Hae-Young Lopilly","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,20]]},"reference":[{"key":"ref_1","first-page":"844","article-title":"Global data on visual impairment in the year 2002","volume":"82","author":"Resnikoff","year":"2004","journal-title":"Bull. 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