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  • Title: The effect of insulin and glucose levels on retinal glial cell activation and pigment epithelium-derived fibroblast growth factor-2.
    Author: Layton CJ, Becker S, Osborne NN.
    Journal: Mol Vis; 2006 Jan 18; 12():43-54. PubMed ID: 16446701.
    Abstract:
    PURPOSE: The diabetic retina exhibits decreases in endogenous nonangiogenic neurotrophins. This study hypothesized that deficiencies in systemic and retinal pigment epithelium-derived (RPE) neurotrophic factors also influence retinal changes in diabetes. METHODS: Diabetes was established in Listar hooded rats with streptozotocin. Reverse transcriptase coupled polymerase chain reaction (RT-PCR) and immunoblotting were used to determine the expression of fibroblast growth factor-2 (FGF-2) in the retina and RPE, and glial fibrillary acid protein (GFAP) in the retina. In addition, primary human RPE cultures and a transformed Müller cell line were used to determine the effect of insulin, glucose, and insulin-like growth factor (IGF) on the expression of these substances. RESULTS: FGF-2 and GFAP were increased in retina, but FGF-2 was decreased in the RPE of diabetic animals. Retinal GFAP correlated with RPE FGF-2 expression in these animals. Insulin produced a dose-dependent increase in FGF-2 in RPE cells and decrease in GFAP in Müller cells grown in 15 mM glucose. In 5 mM glucose, insulin had no effect on expression of either protein. Physiological levels of insulin inhibited changes induced by 15 mM glucose. The effect of 9 nM insulin on each culture was mimicked by 1 nM IGF, and blocked with an IGFR-1 inhibitor. CONCLUSIONS: It is suggested that decreased systemic insulin and high glucose levels contribute to decreased FGF-2 production in the RPE and increased glial cell activation in the diabetic retina. Addition of insulin and IGF act to reverse this effect through the IGFR-1. These mechanisms may contribute to the development of diabetic retinopathy.
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