Activated protein c (Apc) and 3k3a‐apc‐induced regression of choroidal neovascularization (cnv) is accompanied by vascular endothelial growth factor (vegf) reduction

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

Research output: Contribution to journalArticlepeer-review

Abstract

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 di-minishing 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 in-travitreally 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 stain-ing. 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.

Original languageEnglish
Article number358
Pages (from-to)1-13
Number of pages13
JournalBiomolecules
Volume11
Issue number3
DOIs
StatePublished - Mar 2021

Keywords

  • Activated protein C (APC)
  • Choroidal neovascularization (CNV)
  • Mouse model
  • Retina
  • Tie2
  • Vascular endothelial growth factor (VEGF)

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