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R. Srinivasan, A. Basu, J. Maestes, P. McGuire, A. Das; Plasminogen Activator Inhibitor -1 (PAI-1) Facilitates Angiogenesis in a Model of Oxygen Induced Retinopathy. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3451. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
The formation of new retinal blood vessels is a key feature of the pathology of diabetic retinopathy or retinopathy of prematurity. The aim of the present study was to investigate the role of the serine proteinase inhibitor PAI-1 in facilitating retinal new vessel formation.
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 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 investigated using isolated human retinal vascular endothelial cells. The migratory activity of the cells was quantitated in the presence of a PAI-1 neutralizing antibody.
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.
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.
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