{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T12:04:08Z","timestamp":1789473848244,"version":"build-2803163510"},"reference-count":42,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T00:00:00Z","timestamp":1614297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL142975"],"award-info":[{"award-number":["R01 HL142975"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Tel Aviv University Research Authority Meirbaum foundation","award":["0601243983"],"award-info":[{"award-number":["0601243983"]}]},{"DOI":"10.13039\/501100005310","name":"Claire and Am\u00e9d\u00e9e Maratier Institute for the Study of Blindness and Visual Disorders, Tel Aviv University","doi-asserted-by":"publisher","award":["32003197000"],"award-info":[{"award-number":["32003197000"]}],"id":[{"id":"10.13039\/501100005310","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The activated protein C (APC) ability to inhibit choroidal neovascularization (CNV) growth and leakage was recently shown in a murine model. A modified APC, 3K3A-APC, was designed to reduce anticoagulant activity while maintaining full cytoprotective properties, thus diminishing bleeding risk. We aimed to study the ability of 3K3A-APC to induce regression of CNV and evaluate vascular endothelial growth factor (VEGF) role in APC\u2019s activities in the retina. CNV was induced by laser photocoagulation on C57BL\/6J mice. APC and 3K3A-APC were injected intravitreally after verification of CNV presence. CNV volume and vascular penetration were evaluated on retinal pigmented epithelium (RPE)-choroid flatmount by fluorescein isothiocyanate (FITC)-dextran imaging. VEGF levels were measured using immunofluorescence anti-VEGF staining. We found that 3K3A-APC induced regression of pre-existing CNV. VEGF levels, measured in the CNV lesion sites, significantly decreased upon APC and 3K3A-APC treatment. Reduction in VEGF was sustained 14 days post a single APC injection. As 3K3A-APC retained APCs\u2019 activities, we conclude that the anticoagulant properties of APC are not mandatory for APC activities in the retina and that VEGF reduction may contribute to the protective effects of APC and 3K3A-APC. Our results highlight the potential use of 3K3A-APC as a novel treatment for CNV and other ocular pathologies.<\/jats:p>","DOI":"10.3390\/biom11030358","type":"journal-article","created":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T09:47:20Z","timestamp":1614332840000},"page":"358","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Activated Protein C (APC) and 3K3A-APC-Induced Regression of Choroidal Neovascularization (CNV) Is Accompanied by Vascular Endothelial Growth Factor (VEGF) Reduction"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1279-2557","authenticated-orcid":false,"given":"Tami","family":"Livnat","sequence":"first","affiliation":[{"name":"Rabin Medical Center, Ophthalmology Department and Laboratory of Eye Research Felsenstein Medical Research Center, Petah-Tikva 49100, Israel"},{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv 69978, Israel"},{"name":"Sheba Medical Center, The Amalia Biron Thrombosis Research Institute, Tel-Hashomer 52621, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5923-769X","authenticated-orcid":false,"given":"Yehonatan","family":"Weinberger","sequence":"additional","affiliation":[{"name":"Rabin Medical Center, Ophthalmology Department and Laboratory of Eye Research Felsenstein Medical Research Center, Petah-Tikva 49100, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa","family":"Bashir","sequence":"additional","affiliation":[{"name":"Rabin Medical Center, Ophthalmology Department and Laboratory of Eye Research Felsenstein Medical Research Center, Petah-Tikva 49100, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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 49100, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dahlia","family":"Palevski","sequence":"additional","affiliation":[{"name":"Rabin Medical Center, Ophthalmology Department and Laboratory of Eye Research Felsenstein Medical Research Center, Petah-Tikva 49100, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarina","family":"Levy-Mendelovich","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv 69978, Israel"},{"name":"Sheba Medical Center, The Amalia Biron Thrombosis Research Institute, Tel-Hashomer 52621, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gili","family":"Kenet","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv 69978, Israel"},{"name":"Sheba Medical Center, The Amalia Biron Thrombosis Research Institute, Tel-Hashomer 52621, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6652-2667","authenticated-orcid":false,"given":"Ivan","family":"Budnik","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Sechenov First Moscow State Medical University (Sechenov University), 119019 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yael","family":"Nisgav","sequence":"additional","affiliation":[{"name":"Rabin Medical Center, Ophthalmology Department and Laboratory of Eye Research Felsenstein Medical Research Center, Petah-Tikva 49100, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John H.","family":"Griffin","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dov","family":"Weinberger","sequence":"additional","affiliation":[{"name":"Rabin Medical Center, Ophthalmology Department and Laboratory of Eye Research Felsenstein Medical Research Center, Petah-Tikva 49100, Israel"},{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.preteyeres.2015.06.002","article-title":"Molecular pathogenesis of retinal and choroidal vascular diseases","volume":"49","author":"Campochiaro","year":"2015","journal-title":"Prog. 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