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Lori J. Kornberg, Lynn C. Shaw, Polyxenie E. Spoerri, Sergio Caballero, Maria B. Grant; Focal Adhesion Kinase Overexpression Induces Enhanced Pathological Retinal Angiogenesis. Invest. Ophthalmol. Vis. Sci. 2004;45(12):4463-4469. doi: 10.1167/iovs.03-1201.
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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 × 10−9), 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.
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