{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T03:12:21Z","timestamp":1785294741399,"version":"3.55.0"},"reference-count":43,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T00:00:00Z","timestamp":1775088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Corneal alkali burns represent one of the most severe forms of ocular surface injury and frequently result in persistent inflammation, corneal neovascularization, stromal remodeling, and permanent visual impairment. Current therapeutic approaches incompletely control the inflammatory mechanisms that sustain pathological angiogenesis and tissue disorganization. In this study, we evaluated the effects of a transglutaminase-binding fusion protein (FP) in a rat model of alkali-induced corneal injury. Following standardized alkali burns, animals were treated topically with FP, secretory leukocyte protease inhibitor (SLPI), or Buffer. Corneal epithelial healing, opacity, and neovascularization were assessed clinically and by digital image-based quantification, while histological and immunofluorescence analyses were used to evaluate stromal organization and vascular invasion. Molecular mechanisms were investigated by RT-qPCR and Western blot analysis of key inflammatory, angiogenic, and signaling mediators. FP treatment significantly accelerated corneal re-epithelialization, reduced corneal opacity, and markedly attenuated corneal neovascularization compared to SLPI and Buffer controls. These effects were associated with coordinated downregulation of pro-inflammatory cytokines and angiogenic mediators, including TNF-\u03b1, IL-17, VEGF, and cPLA2. Notably, FP suppressed transglutaminase 2 expression and induced early and sustained downregulation of NF-\u03baB pathway components, identifying modulation of an upstream inflammatory pathway central to corneal angiogenesis and stromal remodeling. Collectively, these findings demonstrate that FP effectively limits inflammation-driven corneal neovascularization and tissue remodeling following alkali injury, supporting its potential as a disease-modifying therapeutic strategy for inflammatory ocular surface disorders.<\/jats:p>","DOI":"10.3390\/ijms27073247","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T16:51:02Z","timestamp":1775148662000},"page":"3247","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Downregulation of the Transglutaminase 2\u2013NF-\u03baB Inflammatory Axis by a Fusion Protein of Cementoin and Secretory Leukocyte Protease Inhibitor Reduces Corneal Angiogenesis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8735-8667","authenticated-orcid":false,"given":"Juan Pablo","family":"Salica","sequence":"first","affiliation":[{"name":"Instituto de Investigaciones en Medicina Traslacional (IIMT), Facultad de Ciencias Biom\u00e9dicas, Universidad Austral, and CONICET, Pilar, Buenos Aires B1629, Argentina"},{"name":"Departamento de Oftalmolog\u00eda, Hospital Universitario Austral, Pilar, Buenos Aires B1629, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4116-5875","authenticated-orcid":false,"given":"Mar\u00eda Constanza","family":"Potilinski","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones en Medicina Traslacional (IIMT), Facultad de Ciencias Biom\u00e9dicas, Universidad Austral, and CONICET, Pilar, Buenos Aires B1629, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo","family":"Ortiz","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones en Medicina Traslacional (IIMT), Facultad de Ciencias Biom\u00e9dicas, Universidad Austral, and CONICET, Pilar, Buenos Aires B1629, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7423-2646","authenticated-orcid":false,"given":"Paulo C.","family":"Maffia","sequence":"additional","affiliation":[{"name":"Consejo Nacional de Investigaciones Cientificas y T\u00e9cnicas (CONICET), Buenos Aires C1425, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Guerrieri","sequence":"additional","affiliation":[{"name":"Centro de Estudios Farmacol\u00f3gicos y Bot\u00e1nicos (CEFYBO), Facultad de Medicina, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Universidad de Buenos Aires, Buenos Aires C1121, Argentina"},{"name":"Departamento de Microbiolog\u00eda, Facultad de Medicina, Universidad de Buenos Aires, Parasitolog\u00eda e Inmunolog\u00eda, Buenos Aires C1121, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3084-2500","authenticated-orcid":false,"given":"Eduardo","family":"Chuluyan","sequence":"additional","affiliation":[{"name":"Centro de Estudios Farmacol\u00f3gicos y Bot\u00e1nicos (CEFYBO), Facultad de Medicina, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Universidad de Buenos Aires, Buenos Aires C1121, Argentina"},{"name":"Departamento de Microbiolog\u00eda, Facultad de Medicina, Universidad de Buenos Aires, Parasitolog\u00eda e Inmunolog\u00eda, Buenos Aires C1121, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7502-6323","authenticated-orcid":false,"given":"Juan Eduardo","family":"Gallo","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones en Medicina Traslacional (IIMT), Facultad de Ciencias Biom\u00e9dicas, Universidad Austral, and CONICET, Pilar, Buenos Aires B1629, Argentina"},{"name":"Departamento de Oftalmolog\u00eda, Hospital Universitario Austral, Pilar, Buenos Aires B1629, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2694","DOI":"10.4103\/IJO.IJO_3330_22","article-title":"Demographic profile and clinical characteristics of patients presenting with acute ocular burns","volume":"71","author":"Kate","year":"2023","journal-title":"Indian J. 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