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H. Kim, I.-Y. Chung, B. Park; Simvastatin Suppresses Expression of Angiogenic Factors in the Retina of Rats With Streptozotocin Induced Diabetes. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3333.
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Angiogenic factors such as vascular endothelial growth factor (VEGF), erythropoietin, and angiopoietin play an important role in the pathophysiology of diabetic retinopathy. Increased reactive oxygen species (ROS) are also associated with diabetic retinopathy and expression of VEGF. This study evaluated the effect of a simvastatin on ROS generation and the changes of various angiogenic factors in an experimental diabetic rat retina.
The rats were divided into normal, diabetes mellitus (DM), and simvastatin-treated groups (each group n=10). Diabetes was induced chemically by intraperitoneal injection of streptozotocin in 20 Sprague-Dawley rats. After inducing diabetes, simvastatin (5 mg/kg) was administered to 10 rats orally. The eyeballs were harvested 8 weeks after inducing diabetes. The expressions of VEGF, erythropoietin, angiopoietin 1 & 2, and NADPH oxidase were examined in the rat retina using immunohistochemistry, RT-PCR, and Western blot. Superoxide formation was examined using dihidroethidium (DHE) stain.
DHE analysis showed increased superoxide formation in the retina of the diabetic group, while superoxide formation was decreased in the group treated with simvastatin. Western blot analysis showed that NADPH oxidase was decreased in the diabetic group and was at a normal level in the simvastatin treated group. Treatment with simvastatin blocked hyperglycemia induced increases of VEGF, angiopoietin 2 and erythropoietin shown by immunohistochemistry, RT-PCR, and Western blot analysis.
Superoxide formation may be implicated with expression of angiopoietin and erythropoietin as well as VEGF in diabetic rat retina. Simvastatin treatment induced decreased expression of VEGF, angiopoietin 2 and erythropoietin in diabetic rat retina, which was suspected to be correlated with blockade of superoxide formation.
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