PURPOSE. Focal adhesion kinase (FAK) is involved in processes integral to angiogenesis, such as cell growth, survival, and migration. FAK is activated by angiogenic growth factors, such as insulin-like growth factor (IGF)-I, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF). The study was conducted to determine whether overexpression of FAK or FAK-related nonkinase (FRNK), an inhibitor of FAK, could influence human retinal endothelial cell (HREC) migration and

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... in vivo angiogenesis. METHODS. Migration in response to a combination of growth factors was examined in transfected HRECs overexpressing FAK or FRNK. The effect of FAK or FRNK overexpression on preretinal neovascularization was examined in a mouse model of oxygen-induced retinopathy. RESULTS. Overexpression of FAK in HRECs resulted in a 102% Ϯ 13% increase (P ϭ 1.4 ϫ 10 Ϫ4 ) in cell migration, whereas overexpression of FRNK resulted in a 20% Ϯ 8% decrease (P ϭ 0.01). Overexpression of FAK in mouse eyes led to formation of numerous large vascular tufts resembling glomeruli and a 57% Ϯ 7% increase in preretinal neovascularization (P ϭ 3 ϫ 10 Ϫ9 ), whereas FRNK resulted in a 55% Ϯ 15% reduction (P ϭ 5 ϫ 10 Ϫ5 ). CONCLUSIONS. Modulating the FAK/FRNK system may provide a novel approach to inhibiting pathologic retinal angiogenesis.