Focal adhesion kinase overexpression induces enhanced pathological retinal angiogenesis.
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.
Kornberg
Lori J
LJ
Department of Otolaryngology, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
Shaw
Lynn C
LC
Spoerri
Polyxenie E
PE
Caballero
Sergio
S
Grant
Maria B
MB
D000818:Animals; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D011505:Protein-Tyrosine Kinases / Q000378:metabolism* / Q000494:pharmacology; D015861:Retinal Neovascularization / Q000139:chemically induced / Q000209:etiology*; D014162:Transfection
C113183:FAK-related nonkinase; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; C496051:Ptk2 protein, mouse