Focal adhesion kinase overexpression induces enhanced pathological retinal angiogenesis

Lori J. Kornberg, Lynn C. Shaw, Polyxenie E. Spoerri, Sergio Caballero, Maria B. Grant

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4463-4469
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume45
Issue number12
DOIs
StatePublished - Dec 1 2004

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Focal adhesion kinase overexpression induces enhanced pathological retinal angiogenesis'. Together they form a unique fingerprint.

  • Cite this