TY - JOUR
T1 - Knockout of insulin and IGF-1 receptors on vascular endothelial cells protects against retinal neovascularization
AU - Kondo, Tatsuya
AU - Vicent, David
AU - Suzuma, Kiyoshi
AU - Yanagisawa, Masashi
AU - King, George L.
AU - Holzenberger, Martin
AU - Kahn, C. Ronald
PY - 2003/6
Y1 - 2003/6
N2 - 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.
AB - 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.
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U2 - 10.1172/JCI200317455
DO - 10.1172/JCI200317455
M3 - Article
C2 - 12813019
AN - SCOPUS:0041743158
SN - 0021-9738
VL - 111
SP - 1835
EP - 1842
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 12
ER -