Knockout of insulin and IGF-1 receptors on vascular endothelial cells protects against retinal neovascularization

Tatsuya Kondo, David Vicent, Kiyoshi Suzuma, Masashi Yanagisawa, George L. King, Martin Holzenberger, C. Ronald Kahn

Research output: Contribution to journalArticle

180 Scopus citations

Abstract

Both insulin and IGF-1 have been implicated in control of retinal endothelial cell growth, neovascularization, and diabetic retinopathy. To precisely define the role of insulin and IGF-1 signaling in endothelium in these processes, we have used the oxygen-induced retinopathy model to study mice with a vascular endothelial cell-specific knockout of the insulin receptor (VENIRKO) or IGF-1 receptor (VENIFARKO). Following relative hypoxia, VENIRKO mice show a 57% decrease in retinal neovascularization as compared with controls. This is associated with a blunted rise in VEGF, eNOS, and endothelin-1. By contrast, VENIFARKO mice show only a 34% reduction in neovascularization and a very modest reduction in mediator generation. These data indicate that both insulin and IGF-1 signaling in endothelium play a role in retinal neovascularization through the expression of vascular mediators, with the effect of insulin being most important in this process.

Original languageEnglish (US)
Pages (from-to)1835-1842
Number of pages8
JournalJournal of Clinical Investigation
Volume111
Issue number12
DOIs
StatePublished - Jun 1 2003

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ASJC Scopus subject areas

  • Medicine(all)

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