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Activated protein C induces suppression and regression of choroidal neovascularization– A murine model

Livnat T., Weinberger Y., Budnik I. A., Deitch I., Dahbash M., Sella R., Dardik R., Kenet G., Nisgav Y., Weinberger D.
Experimental Eye Research
Vol.186, Num.107695
Опубликовано: 2019
Тип ресурса: Статья

DOI:10.1016/j.exer.2019.107695

Аннотация:
Activated protein C (APC) exerts diverse cell signaling pathways which results in multiple distinct cytoprotective actions. These include anti-apoptotic and anti-inflammatory activities and stabilization of endothelial and epithelial barriers. We studied the ability of APC to inhibit the leakage and the growth of newly formed as well as pre-existing choroidal neovascularization (CNV) and examined the ability of APC to stabilize the Retinal Pigmented Epithelium (RPE). We explored the contribution of Tie2 receptor to the protective effects of APC. CNV was induced by laser photocoagulation in C57BL/6J mice. APC was injected intravitreally immediately or 7 days after CNV induction. Neovascularization was evaluated on RPE-choroidal flatmounts using FITC-dextran perfusion and CD31 immunofluorescence. CNV leakage was measured by fluorescein angiography (FA). The ability of APC to stabilize the RPE barrier was evaluated in-vitro by dextran permeability and zonula occludens 1 (ZO1) immunostaini
Ключевые слова:
Activated protein C; Blood retinal barrier; Choroidal neovascularization; Laser induced CNV; Mice; Zonula occludens 1
activated protein C; angiopoietin receptor; platelet endothelial cell adhesion molecule 1; protein ZO1; antiinfective agent; drotrecogin; protein C; protein ZO1; recombinant protein; TJP1 protein, human; Tjp1 protein, mouse; animal cell; animal experiment; animal model; animal tissue; Article; cell culture; fluorescence angiography; immunofluorescence; immunohistochemistry; in vitro study; in vivo study; laser coagulation; mouse; nonhuman; priority journal; retinal pigment epithelium; subretinal neovascularization; animal; C57BL mouse; capillary permeability; cell membrane permeability; choroid; disease model; dose response; drug effect; human; indirect fluorescent antibody technique; male; metabolism; pathophysiology; subretinal neovascularization; vascularization; Animals; Anti-Infective Agents; Capillary Permeability; Cell Membrane Permeability; Choroid; Choroidal Neovascularization; Disease Models, Animal; Dose-Response Relationship, Drug; Fluorescein Angiography; Fluorescent Antib
Язык текста: Английский
ISSN: 1096-0007
Livnat T.
Weinberger Y.
Budnik I. A. Ivan Aleksandrovich 1983-
Deitch I.
Dahbash M.
Sella R.
Dardik R.
Kenet G.
Nisgav Y.
Weinberger D.
Ливнат Т.
Wеинбергер Y.
Будник И. А. Иван Александрович 1983-
Деитч И.
Дахбаш М.
Селла Р.
Дардик Р.
Кенет Г.
Нисгав Y.
Wеинбергер Д.
Activated protein C induces suppression and regression of choroidal neovascularization– A murine model
Текст визуальный непосредственный
Experimental Eye Research
Academic Press
Vol.186 Num.107695
2019
Статья
Activated protein C Blood retinal barrier Choroidal neovascularization Laser induced CNV Mice Zonula occludens 1
activated protein C angiopoietin receptor platelet endothelial cell adhesion molecule 1 protein ZO1 antiinfective agent drotrecogin protein C protein ZO1 recombinant protein TJP1 protein, human Tjp1 protein, mouse animal cell animal experiment animal model animal tissue Article cell culture fluorescence angiography immunofluorescence immunohistochemistry in vitro study in vivo study laser coagulation mouse nonhuman priority journal retinal pigment epithelium subretinal neovascularization animal C57BL mouse capillary permeability cell membrane permeability choroid disease model dose response drug effect human indirect fluorescent antibody technique male metabolism pathophysiology subretinal neovascularization vascularization Animals Anti-Infective Agents Capillary Permeability Cell Membrane Permeability Choroid Choroidal Neovascularization Disease Models, Animal Dose-Response Relationship, Drug Fluorescein Angiography Fluorescent Antib
Activated protein C (APC) exerts diverse cell signaling pathways which results in multiple distinct cytoprotective actions. These include anti-apoptotic and anti-inflammatory activities and stabilization of endothelial and epithelial barriers. We studied the ability of APC to inhibit the leakage and the growth of newly formed as well as pre-existing choroidal neovascularization (CNV) and examined the ability of APC to stabilize the Retinal Pigmented Epithelium (RPE). We explored the contribution of Tie2 receptor to the protective effects of APC. CNV was induced by laser photocoagulation in C57BL/6J mice. APC was injected intravitreally immediately or 7 days after CNV induction. Neovascularization was evaluated on RPE-choroidal flatmounts using FITC-dextran perfusion and CD31 immunofluorescence. CNV leakage was measured by fluorescein angiography (FA). The ability of APC to stabilize the RPE barrier was evaluated in-vitro by dextran permeability and zonula occludens 1 (ZO1) immunostaini