{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:22:55Z","timestamp":1785435775860,"version":"3.56.0"},"reference-count":46,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"publisher","award":["W81XWH2110740"],"award-info":[{"award-number":["W81XWH2110740"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"award":["W81XWH2110740"],"award-info":[{"award-number":["W81XWH2110740"]}],"id":[{"id":"https:\/\/ror.org\/0447fe631","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/04drjs621","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Severe full-thickness corneal lacerations disrupt the tight cellular and extracellular matrix (ECM) organization required for corneal transparency. Following injury, an influx of transforming growth factor beta (TGF\u03b2) into the corneal stroma signals the formation of haze-inducing myofibroblasts, resulting in excessive stromal remodeling and corneal haze. We hypothesized that MasR activation using NorLeu3Angiotensin (1-7) (NLE) engages the pro-resolving arm of the renin\u2013angiotensin system (RAS) to minimize fibrotic corneal repair. In this study, 6 mm stellate-shaped, full-thickness corneal lacerations were induced in New Zealand Black (NZB) rabbits and treated with topical vehicle, or 0.1%, 0.3%, or 0.45% NLE. Corneal healing was evaluated using noninvasive corneal imaging, histology, and the gene expression of RAS- and fibrosis-related targets (MasR, AT1R, TGF\u03b2R1). Corneal imaging revealed significantly decreased corneal haze (p &lt; 0.05) and increased keratocyte density with 0.1% NLE treatment (p &lt; 0.05). Immunofluorescence showed significantly reduced \u03b1-smooth muscle actin (\u03b1SMA), indicating decreased myofibroblast formation (p &lt; 0.05). Additionally, 0.1% NLE reduced stromal TGF\u03b2R1, suggesting that NLE mediates its activity by disrupting the TGF\u03b2\/TGF\u03b2R axis. MasR and AT1R gene expression were downregulated, which contributes to a reduction in fibrosis. Collectively, these findings suggest that the NLE activation of MasR modulates RAS and TGF\u03b2\/TGF\u03b2R signaling to reduce myofibroblast activity and fibrosis following severe corneal trauma.<\/jats:p>","DOI":"10.3390\/ijms27083565","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T15:14:12Z","timestamp":1776352452000},"page":"3565","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Administration of Topical NorLeu3Angiotensin(1-7) Minimizes Fibrotic Corneal Healing in Stellate Wound: A 28-Day Study"],"prefix":"10.3390","volume":"27","author":[{"given":"Catherine","family":"Chester","sequence":"first","affiliation":[{"name":"Titus Family Department of Clinical Pharmacy, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1283-1744","authenticated-orcid":false,"given":"Edgar Alejandro","family":"Moreno-Diaz","sequence":"additional","affiliation":[{"name":"Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA"},{"name":"USC Ginsburg Institute for Biomedical Therapeutics, University of Southern California, Los Angeles, CA 90089, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyuan","family":"Hu","sequence":"additional","affiliation":[{"name":"Titus Family Department of Clinical Pharmacy, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brianna","family":"Chen","sequence":"additional","affiliation":[{"name":"Titus Family Department of Clinical Pharmacy, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maram","family":"Alshammari","sequence":"additional","affiliation":[{"name":"Titus Family Department of Clinical Pharmacy, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark S.","family":"Humayun","sequence":"additional","affiliation":[{"name":"Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA"},{"name":"USC Ginsburg Institute for Biomedical Therapeutics, University of Southern California, Los Angeles, CA 90089, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Carlos Martinez","family":"Camarillo","sequence":"additional","affiliation":[{"name":"Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA"},{"name":"USC Ginsburg Institute for Biomedical Therapeutics, University of Southern California, Los Angeles, CA 90089, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5941-6690","authenticated-orcid":false,"given":"Stan G.","family":"Louie","sequence":"additional","affiliation":[{"name":"Titus Family Department of Clinical Pharmacy, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089, USA"},{"name":"USC Ginsburg Institute for Biomedical Therapeutics, University of Southern California, Los Angeles, CA 90089, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.brainresbull.2009.05.019","article-title":"Corneal transparency: Genesis, maintenance and dysfunction","volume":"81","author":"Qazi","year":"2010","journal-title":"Brain Res. Bull."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"190","DOI":"10.4103\/ijo.IJO_646_17","article-title":"Anatomy of cornea and ocular surface","volume":"66","author":"Sridhar","year":"2018","journal-title":"Indian. J. 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