Activated Protein C (APC) and 3K3A-APC-Induced Regression of Choroidal Neovascularization (CNV) Is Accompanied by Vascular Endothelial Growth Factor (VEGF) Reduction

Autor: Tami Livnat, Yehonatan Weinberger, José A. Fernández, Alaa Bashir, Gil Ben-David, Dahlia Palevski, Sarina Levy-Mendelovich, Gili Kenet, Ivan Budnik, Yael Nisgav, John H. Griffin, Dov Weinberger
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Biomolecules, Vol 11, Iss 3, p 358 (2021)
Druh dokumentu: article
ISSN: 2218-273X
DOI: 10.3390/biom11030358
Popis: 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’s 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’ 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.
Databáze: Directory of Open Access Journals
Nepřihlášeným uživatelům se plný text nezobrazuje