Plasminogen Activator Inhibitor-1 (PAI-1) Facilitates Retinal Angiogenesis in a Model of Oxygen-Induced Retinopathy

Abstract

Purpose Angiogenesis, or the formation of new retinal blood vessels is a key feature of many proliferative retinal diseases including diabetic retinopathy, retinal vein occlusions, and retinopathy of prematurity. The aim of the present study was to investigate the role of the serine proteinase inhibitor PAI-1 in facilitating retinal angiogenesis. Methods The temporal expression of PAI-1 was examined by real time PCR, western blotting and immunohistochemistry in retinal tissues from mice with oxygen-induced retinopathy. The requirement for PAI-1 in facilitating the retinal angiogenic response in this model was examined by quantitating the angiogenic response using both wildtype and PAI-1 null mice. The mechanism by which PAI-1 mediates angiogenesis was further investigated using isolated human retinal vascular endothelial cells. Results PAI-1 expression is up regulated in the retina of mice with oxygen-induced retinopathy. This coincides with a significant increase in the expression of vitronectin in the retina of the experimental mice. There was significant reduction in the angiogenic response of PAI-1−/− mice as compared to wild type mice. PAI-1 promotes endothelial cell migration in vitro and facilitates migration of cells on a vitronectin substrate by regulating αv integrin cell surface expression. Conclusions These observations suggest a role for PAI-1 during retinal angiogenesis and point to a potential new therapeutic target in the prevention or treatment of retinal neovascularization seen in many ocular diseases.

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“…PAI-1 is involved in cancer angiogenesis, metastasis and promotes angiogenesis by stimulating EC migration toward fibronectin [60]. It also plays a role during retinal angiogenesis [61] and has been demonstrated to support angiogenesis in cancer. Geis et al .…”

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“…This suggests that Malme3M R cells may enhance the angiogenic potential of human endothelial cells via angiogenic factors such as VEGF and PAI-1. PAI-1 facilitates retinal angiogenesis (34) and is necessary for sonic hedgehog-induced cerebral angiogenesis (35). VEGF-B binds to VEGFRI and regulates PAI-1 activity (36).…”

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“…4A), which confirmed that HA did not require VEGF to promote angiogenesis. PAI-1 protects endothelial cells from Fas-mediated apoptosis (Bajou et al, 2008), and facilitates retinal angiogenesis (Basu et al, 2009). These reports indicate the potential role of PAI-1 in angiogenesis.…”