Study On The Effect Of Insulin On Diabetic Retinopathy And The Meachanisms

Diabetic retinopathy is a serious complication of diabetes. In developed countries, diabetic retinopathy is a main cause of bindness. With the development of economy and improvement of living levels, the prevalence of DR increases promptly. The precludsion and treatment of DR has been an important task of ophthalmologist and epidemic specialist.Hyperglycemia is the primary causative factor of DR, therefore, blood glucose control is very important in treatment of diabetes and DR. Insulin is commonly used in control blood glucose. However, Clinical trials have demonstrated that acute intensive insulin therapy causes a transient worsening of diabetic retinopathy in type 1 and type 2 diabetes patients. Insulin treatment is known epidemiologically as an independent risk factor for the progression of diabetic retinopathy. The mechanisms underlying remain unknown. Recently, insulin induced VEGF up regulation was reported to contribute to the progression of DR.To study the role and mechanisms of insulin in DR, the present studies investigate the effect and mechanisms of insulin on VEGF mRNA and protein expression, the effect of insulin on ROS production and apoptosis in BREC exposed to normal and high glucose; the effect and mechanisms of insulin on VEGF mRNA and protein expression in STZ-induced diabetic rats. VEGF mRNA was assaied by real-time PCR; VEGF protein was assaied by immunohistochemistry, HUVEC proliferation assay and western blot. ROS was stained with H2DCFDA and observed by laser scanning confocal microscope and flow cytometry. Cell apoptosis was assaied by flow cytometry.Insulin significantly increase VEGF mRNA and protein expression in vitro and vivo at normal glucose, but can't increase VEGF mRNA and protein expression in vitro and vivo at high glucose. In high glucose, insulin induced VEGF expression through PI-3K. Insulin significantly increases ROS production in BREC at both normal and high glucose. In addition, a combined effect of insulin and high glucose on the intracellular ROS production is significantly higher than insulin or high glucose alone. Insulin can significantly inhibit BREC apoptosis.The results of present studies suggest high glucose attenuate insulin induced VEGF mRNA and protein expression. Therefore, VEGF may be not the major factor results in the transient worsening of diabetic retinopathy after acute insulin therapy in diabetes. Insulin induced high concentration of ROS may be one of main causes of the transient worsening of diabetic retinopathy.