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

23 Citations (Scopus)

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 2004
Externally publishedYes

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Pathologic Neovascularization
Focal Adhesion Protein-Tyrosine Kinases
Cell Movement
Intercellular Signaling Peptides and Proteins
Angiogenesis Inducing Agents
Fibroblast Growth Factor 2
Insulin-Like Growth Factor I
Vascular Endothelial Growth Factor A
Blood Vessels
Cell Survival
Endothelial Cells
FAK-related nonkinase
Oxygen

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Focal adhesion kinase overexpression induces enhanced pathological retinal angiogenesis. / Kornberg, Lori J.; Shaw, Lynn C.; Spoerri, Polyxenie E.; Caballero, Sergio; Grant, Maria B.

In: Investigative Ophthalmology and Visual Science, Vol. 45, No. 12, 12.2004, p. 4463-4469.

Research output: Contribution to journalArticle

Kornberg, Lori J. ; Shaw, Lynn C. ; Spoerri, Polyxenie E. ; Caballero, Sergio ; Grant, Maria B. / Focal adhesion kinase overexpression induces enhanced pathological retinal angiogenesis. In: Investigative Ophthalmology and Visual Science. 2004 ; Vol. 45, No. 12. pp. 4463-4469.
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