TY - JOUR
T1 - Activated protein c (Apc) and 3k3a‐apc‐induced regression of choroidal neovascularization (cnv) is accompanied by vascular endothelial growth factor (vegf) reduction
AU - Livnat, Tami
AU - Weinberger, Yehonatan
AU - Fernández, José A.
AU - Bashir, Alaa
AU - Ben‐david, Gil
AU - Palevski, Dahlia
AU - Levy‐mendelovich, Sarina
AU - Kenet, Gili
AU - Budnik, Ivan
AU - Nisgav, Yael
AU - Griffin, John H.
AU - Weinberger, Dov
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/3
Y1 - 2021/3
N2 - 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.
AB - 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.
KW - Activated protein C (APC)
KW - Choroidal neovascularization (CNV)
KW - Mouse model
KW - Retina
KW - Tie2
KW - Vascular endothelial growth factor (VEGF)
UR - http://www.scopus.com/inward/record.url?scp=85101574656&partnerID=8YFLogxK
U2 - 10.3390/biom11030358
DO - 10.3390/biom11030358
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C2 - 33652861
AN - SCOPUS:85101574656
SN - 2218-273X
VL - 11
SP - 1
EP - 13
JO - Biomolecules
JF - Biomolecules
IS - 3
M1 - 358
ER -