OBJECTIVE

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 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% +/- 13% increase (P = 1.4 x 10(-4)) in cell migration, whereas overexpression of FRNK resulted in a 20% +/- 8% decrease (P = 0.01). Overexpression of FAK in mouse eyes led to formation of numerous large vascular tufts resembling glomeruli and a 57% +/- 7% increase in preretinal neovascularization (P = 3 x 10(-9)), whereas FRNK resulted in a 55% +/- 15% reduction (P = 5 x 10(-5)).

CONCLUSIONS

Modulating the FAK/FRNK system may provide a novel approach to inhibiting pathologic retinal angiogenesis.