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 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 × 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 × 1O-9), whereas FRNK resulted in a 55% ± 15% reduction (P = 5 × 10-5). CONCLUSIONS. Modulating the FAK/FRNK system may provide a novel approach to inhibiting pathologic retinal angiogenesis.
ASJC Scopus subject areas
- Sensory Systems
- Cellular and Molecular Neuroscience