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Knockout of insulin and IGF-1 receptors on vascular endothelial cells protects against retinal neovascularization.
- Source :
-
The Journal of clinical investigation [J Clin Invest] 2003 Jun; Vol. 111 (12), pp. 1835-42. - Publication Year :
- 2003
-
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.
- Subjects :
- Animals
Diabetic Retinopathy etiology
Diabetic Retinopathy pathology
Diabetic Retinopathy physiopathology
Disease Models, Animal
Endothelial Growth Factors physiology
Endothelin-1 physiology
Endothelium, Vascular pathology
Endothelium, Vascular physiopathology
Humans
Hypoxia pathology
Hypoxia physiopathology
Insulin physiology
Intercellular Signaling Peptides and Proteins physiology
Lymphokines physiology
Mice
Mice, Inbred C57BL
Mice, Inbred DBA
Mice, Knockout
Nitric Oxide Synthase physiology
Nitric Oxide Synthase Type II
Nitric Oxide Synthase Type III
Receptor, IGF Type 1 genetics
Receptor, IGF Type 1 physiology
Receptor, Insulin genetics
Receptor, Insulin physiology
Signal Transduction
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
Diabetic Retinopathy prevention & control
Neovascularization, Pathologic
Receptor, IGF Type 1 deficiency
Receptor, Insulin deficiency
Retinal Vessels pathology
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9738
- Volume :
- 111
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- The Journal of clinical investigation
- Publication Type :
- Academic Journal
- Accession number :
- 12813019
- Full Text :
- https://doi.org/10.1172/JCI17455