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

Jesús Ruberte, Eduard Ayuso, Marc Navarro, Ana Carretero, Víctor Nacher, Virginia Haurigot, Mónica George, Cristina Llombart, Alba Casellas, Cristina Costa, Assumpció Bosch, Fatima Bosch

Research output: Contribution to journalArticleResearchpeer-review

144 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)1149-1157
JournalJournal of Clinical Investigation
Volume113
Issue number8
DOIs
Publication statusPublished - 1 Jan 2004

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