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PMID: 15085194 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Increased ocular levels of IGF-1 in transgenic mice lead to diabetes-like eye disease.

The Journal of clinical investigation ·Vol. 113 ·No. 8 ·2004-04-00 ·Pages 1149-57

Ruberte J, Ayuso E, Navarro M, Carretero A, Nacher V, Haurigot V, George M, Llombart C, Casellas A, Costa C, Bosch A, Bosch F

Abstract

IGF-1 has been associated with the pathogenesis of diabetic retinopathy, although its role is not fully understood. Here we show that normoglycemic/normoinsulinemic transgenic mice overexpressing IGF-1 in the retina developed most alterations seen in human diabetic eye disease. A paracrine effect of IGF-1 in the retina initiated vascular alterations that progressed from nonproliferative to proliferative retinopathy and retinal detachment. Eyes from 2-month-old transgenic mice showed loss of pericytes and thickening of basement membrane of retinal capillaries. In mice 6 months and older, venule dilatation, intraretinal microvascular abnormalities, and neovascularization of the retina and vitreous cavity were observed. Neovascularization was consistent with increased IGF-1 induction of VEGF expression in retinal glial cells. In addition, IGF-1 accumulated in aqueous humor, which may have caused rubeosis iridis and subsequently adhesions between the cornea and iris that hampered aqueous humor drainage and led to neovascular glaucoma. Furthermore, all transgenic mice developed cataracts. These findings suggest a role of IGF-1 in the development of ocular complications in long-term diabetes. Thus, these transgenic mice may be used to study the mechanisms that lead to diabetes eye disease and constitute an appropriate model in which to assay new therapies.

MeSH Terms
Animals Cataract/etiology Diabetic Retinopathy/etiology Glaucoma, Neovascular/etiology Glial Fibrillary Acidic Protein/analysis Immunohistochemistry Insulin-Like Growth Factor I/analysis,physiology Mice Mice, Inbred C57BL Mice, Transgenic Retina/metabolism Vascular Endothelial Growth Factor A/analysis
Chemicals
Glial Fibrillary Acidic Protein Vascular Endothelial Growth Factor A Insulin-Like Growth Factor I
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Ruberte Jesús
Center of Animal Biotechnology and Gene Therapy, Department of Animal Health and Anatomy, School of Veterinary Medicine, Universitat Autònoma de Bellaterra, Spain.
Ayuso Eduard
Navarro Marc
Carretero Ana
Nacher Víctor
Haurigot Virginia
George Mónica
Llombart Cristina
Casellas Alba
Costa Cristina
Bosch Assumpció
Bosch Fatima
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI19478
Published
2004-04-00
Pages
1149-57
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC385397
Subset
IM
External Links
PubMed source DOI: 10.1172/JCI19478 PMC Full Text View journal details
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