Tissue plasminogen activator as an anti‐angiogenic agent in experimental laser‐induced choroidal neovascularization

Abstract

AbstractPurpose Tissue plasminogen activator (tPA) is a fibrinolytic compound, utilized originally to treat embolic or thrombotic stroke and as an adjuvant for displacement of submacular hemorrhage. The purpose of this study is to investigate anti‐angiogenic effects of tPA on experimental laser‐induced choroidal neovascularization (CNV) in mice.Methods CNV was induced by laser injury in C57BL/6J mice, and intravitreal injection of tPA (4 or 40 IU/µl) or PBS was performed immediately after laser injury. Fluorescein angiography was performed 7 days after laser treatment to grade fluorescein leakage. And CNV volumes were measured by confocal evaluation of Isolectin B4 staining of RPE‐choroid flatmounts. The expression of fibrin on day 3 was observed by immunostaining.Results Fluorescein leakage was inhibited by tPA in a dose‐dependent manner, and a significant difference was found with tPA (40 IU/ µl) compared with PBS (p=0.02). A dose‐dependent suppression of CNV volume was also observed by tPA, and there was a significant differences between tPA (40 IU/µl) (208988  52456 µm3) and PBS (386902  103060 µm3, p<0.01). The expression of fibrin was reduced in eyes treated with tPA.Conclusion Intravitreal injection of tPA reduced the expression of fibrin and significantly suppressed laser‐induced CNV in mice. These findings suggested that tPA might be anti‐angiogenic and have a potential as an adjuvant to anti‐vascular endothelial growth factor therapy.