VEGF is major stimulator in model of choroidal neovascularization

N. Kwak, N. Okamoto, J. M. Wood, Peter A Campochiaro

Research output: Contribution to journalArticle

Abstract

Purpose. Vascular endothelial growth factor (VEGF) is upregulated by hypoxia and is a major stimulatory factor for retinal neovascularization in ischemic retinopathies such as diabetic retinopathy. This study sought to determine if VEGF is a stimulatory factor in a murine model of choroidal neovascularization (CNV). Methods. Mice with laser-induced ruptures in Bruch's membrane were treated with vehicle alone; a drug that inhibits both VEGF and platelet-derived growth factor (PDGF) receptor kinases; a drug that inhibits PDGF, but not VEGF receptor kinase; or genistein, a nonspecific kinase inhibitor. After two weeks, CNV was quantified and compared. Results. Blockade of phosphorylation by VEGF and PDGF receptors caused dramatic, almost complete inhibition of CNV. Genistein also had an inhibitory effect, but less so than the VEGF/PDGF receptor blocker. Blockade of phosphorylation by PDGF receptors, but not VEGF receptors, had no significant effect on CNV. Conclusions. These data and our previous study, which demonstrated that a kinase inhibitor that blocks VEGF and PDGF receptors and several isoforms of protein kinase C causing dramatic inhibition of CNV, suggest that VEGF signaling plays a critical role in the development of CNV in this model. If safety is established, the effect of inhibiting VEGF receptor kinase activity should be investigated in patients with CNV.

Original languageEnglish (US)
Pages (from-to)3158-3164
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume41
Issue number10
StatePublished - 2000

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Choroidal Neovascularization
Platelet-Derived Growth Factor Receptors
Vascular Endothelial Growth Factor A
Phosphotransferases
Vascular Endothelial Growth Factor Receptor
Genistein
Phosphorylation
Retinal Neovascularization
Bruch Membrane
Platelet-Derived Growth Factor
Diabetic Retinopathy
Pharmaceutical Preparations
Protein Kinase C
Rupture
Protein Isoforms
Lasers
Safety

ASJC Scopus subject areas

  • Ophthalmology

Cite this

VEGF is major stimulator in model of choroidal neovascularization. / Kwak, N.; Okamoto, N.; Wood, J. M.; Campochiaro, Peter A.

In: Investigative Ophthalmology and Visual Science, Vol. 41, No. 10, 2000, p. 3158-3164.

Research output: Contribution to journalArticle

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Y1 - 2000

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