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B. Cho, D.P. Hainsworth, L. Reneker; Insulin Can Stimulate Vascular Cell Growth in the Eye of Transgenic Mice . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3898.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Diabetic retinopathy (DR), a blinding complication of diabetes, is thought to be caused by changes in the retinal vasculature. Insulin–like growth factor (IGF) has been implicated in the development of DR. IGF–1 over–expression in the eyes of transgenic mice causes changes characteristic of DR including expression of vascular endothelial growth factor (VEGF). Insulin, the mainstay of glucose control in diabetics, has similar biological functions as IGF–1. Our purpose was to examine the effects of insulin on ocular vasculature system development in transgenic mice. Methods: Transgenic mice that over–express insulin in the lens were examined by histology, scanning electron microscopy (SEM), and immunohistochemical staining. The levels of VEGF and hypoxia inducible factor (HIF)–1α mRNA were measured by semi–quantitative reverse transcriptase (RT)–PCR. Results: Six transgenic lines expressing variable levels of insulin were examined. Transgenic mice displayed abnormalities in the tunica vasculosa lentis (TVL) surrounding the lens. In contrast to wild–type, transgenic mice demonstrated increased and persistent development of the TVL. SEM demonstrated increased vessel density, branching, and pericytes in the TVL of the transgenic mice. Additionally, it was found that elevated levels of insulin led to increased expression of VEGF. Conclusions: Insulin, like IGF–1, can stimulate vascular growth in the eye. Interestingly, our findings suggest a mechanism for the transient worsening of DR that occurs with intensive insulin treatment as observed in the Diabetes Control and Complications Trial (DCCT). We propose that insulin, like IGF–1, may play a role in the development of DR.
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