{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T22:19:56Z","timestamp":1772489996730,"version":"3.50.1"},"reference-count":55,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T00:00:00Z","timestamp":1687737600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Claire and Amedee Maratier Institute grant for the Study of Blindness and Visual Disorders, Faculty of Medicine, Tel Aviv University","award":["R01HL142975"],"award-info":[{"award-number":["R01HL142975"]}]},{"name":"National Institutes of Health","award":["R01HL142975"],"award-info":[{"award-number":["R01HL142975"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>3K3A-Activated Protein C (APC) is a recombinant variant of the physiological anticoagulant APC with cytoprotective properties and reduced bleeding risks. We studied the potential use of 3K3A-APC as a multi-target therapeutic option for choroidal neovascularization (CNV), a common cause of vision loss in age-related macular degeneration. CNV was induced by laser photocoagulation in a murine model, and 3K3A-APC was intravitreally injected. The impact of 3K3A-APC treatment on myeloid and microglia cell activation and recruitment and on NLRP3 inflammasome, IL-1\u03b2, and VEGF levels was assessed using cryosection, retinal flat-mount immunohistochemistry and vascular imaging. Additionally, we evaluated the use of fluorescein angiography as a surrogate marker for in vivo evaluation of the efficacy of 3K3A-APC treatment against leaking CNV lesions. Our results demonstrated that 3K3A-APC treatment significantly reduced the accumulation and activation of myeloid cells and microglia in the CNV area and decreased the NLRP3 and IL-1\u03b2 levels at the CNV site and the surrounding retina. Furthermore, 3K3A-APC treatment resulted in leakage regression and CNV growth suppression. These findings indicate that the anti-inflammatory activities of 3K3A-APC contribute to CNV inhibition. Our study suggests the potential use of 3K3A-APC as a novel multi-target treatment for CNV.<\/jats:p>","DOI":"10.3390\/ijms241310642","type":"journal-article","created":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T03:14:56Z","timestamp":1687749296000},"page":"10642","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["3K3A-Activated Protein C Inhibits Choroidal Neovascularization Growth and Leakage and Reduces NLRP3 Inflammasome, IL-1\u03b2, and Inflammatory Cell Accumulation in the Retina"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5923-769X","authenticated-orcid":false,"given":"Yehonatan","family":"Weinberger","sequence":"first","affiliation":[{"name":"Rabin Medical Center, Ophthalmology Department and Laboratory of Eye Research Felsenstein Medical Research Center, Petah-Tikva 5251108, Israel"},{"name":"Faculty of Medicine, Tel Aviv University, Tel-Aviv 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivan","family":"Budnik","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, The University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yael","family":"Nisgav","sequence":"additional","affiliation":[{"name":"Rabin Medical Center, Ophthalmology Department and Laboratory of Eye Research Felsenstein Medical Research Center, Petah-Tikva 5251108, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9661-5680","authenticated-orcid":false,"given":"Dahlia","family":"Palevski","sequence":"additional","affiliation":[{"name":"Rabin Medical Center, Ophthalmology Department and Laboratory of Eye Research Felsenstein Medical Research Center, Petah-Tikva 5251108, Israel"},{"name":"Faculty of Medicine, Tel Aviv University, Tel-Aviv 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9993-1005","authenticated-orcid":false,"given":"Gil","family":"Ben-David","sequence":"additional","affiliation":[{"name":"Rabin Medical Center, Ophthalmology Department and Laboratory of Eye Research Felsenstein Medical Research Center, Petah-Tikva 5251108, Israel"},{"name":"Faculty of Medicine, Tel Aviv University, Tel-Aviv 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0804-1865","authenticated-orcid":false,"given":"Jos\u00e9 A.","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shany Nivinsky","family":"Margalit","sequence":"additional","affiliation":[{"name":"Rabin Medical Center, Ophthalmology Department and Laboratory of Eye Research 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Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dov","family":"Weinberger","sequence":"additional","affiliation":[{"name":"Rabin Medical Center, Ophthalmology Department and Laboratory of Eye Research Felsenstein Medical Research Center, Petah-Tikva 5251108, Israel"},{"name":"Faculty of Medicine, Tel Aviv University, Tel-Aviv 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John H.","family":"Griffin","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1279-2557","authenticated-orcid":false,"given":"Tami","family":"Livnat","sequence":"additional","affiliation":[{"name":"Rabin Medical Center, Ophthalmology Department and Laboratory of Eye Research Felsenstein Medical Research Center, Petah-Tikva 5251108, Israel"},{"name":"Faculty of Medicine, Tel Aviv 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