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P. C. Kothary, H. Shah, R. Albeiruti, V. Desai, M. A. Del Monte; Insulin Induces Fibroblast Growth Factor 2 Synthesis in Human Retinal Pigment Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1355.
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Human retinal pigment epithelial cells (hRPE) play an important role in pathogenesis of pre-retinal membrane formation in proliferative diabetic retinopathy (PDR). Since insulin is a mitogen for hRPE cells and insulin therapy can be associated with transient worsening of retinopathy, we investigated the effect of insulin on fibroblast growth factor 2 (FGF2), a growth factor found in hRPE cells within neovascular pre-retinal membranes from PDR patients.
Primary hRPE cell cultures were established from human eyes obtained from the Michigan Eye Bank. Cell proliferation was determined by the trypan blue exclusion method (T) and 3H-thymidine incorporation (3H-thy). Antibodies specific for FGF2 were used for 14C-methionine-FGF2 immuno-precipitation and FGF2 identification by immuno-histochemical studies. PD98059, a MAP kinase pathway inhibitor, was also used to study signaling pathways. Data were analyzed by Student 't' test.
Insulin (0-5 Âµg/ml) stimulates proliferation of hRPE cells in a dose dependent manner as determined by T and 3H-thy. Insulin (0-5 Âµg/ml) also stimulates 14C-methionine-FGF 2 synthesis in hRPE cells in a dose dependent manner. PD98059 inhibited FGF2 synthesis in hRPE cells (402.0Â±99.3 vs. 758.3Â±214.0, CPMÂ±SEM, n=5, p<0.05). PD98059 also significantly inhibited T in hRPE cells (2.96Â±0.83 vs. 18.95Â±2.20, Cells/0.1 ÂµlÂ±SEM, n=3, pâ¤0.05). Immuno-histochemical studies showed increased immuno-reactivity of FGF2 in hRPE cells exposed to insulin, and this increase was blocked by exposure to PD98059.
Insulin stimulates cell proliferation and FGF2 synthesis in hRPE cells. PD98059, a MAP kinase inhibitor, inhibits FGF2 synthesis as well as cell proliferation in hRPE cells. Insulin induced FGF2 synthesis in hRPE cells may play role in the worsening of retinopathy during insulin therapy in patients with diabetes.
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