title: Focal adhesion kinase overexpression induces enhanced pathological retinal angiogenesis.
abstract: 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.
authors.affiliation: Department of Otolaryngology, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Lori J
authors.initials: LJ
authors.lastname: Kornberg
authors.forename: Lynn C
authors.initials: LC
authors.lastname: Shaw
authors.forename: Polyxenie E
authors.initials: PE
authors.lastname: Spoerri
authors.forename: Sergio
authors.initials: S
authors.lastname: Caballero
authors.forename: Maria B
authors.initials: MB
authors.lastname: Grant
mesh_terms: 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
chemical_list: 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