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H. Kim, H. Lee, D. Hur; Effect of Lipoic Acid on Expression of Angiogenic Factors in Diabetic Rat Retina. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2946.
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Angiogenic factors such as vascular endothelial growth factor (VEGF), erythropoietin, and angiopoietin play an important role in the development of diabetic retinopathy. Reactive oxygen species (ROS) are also increased in diabetes and induce expression of VEGF. This study evaluated the effect of a lipoic acid on ROS formation and the simultaneous changes of several angiogenic factors in an experimental diabetic rat retina.
Diabetes was induced chemically by intraperitoneal injection of streptozotocin in 20 Sprague-Dawley rats. After inducing diabetes, lipoic acid (10 mg/kg) was administered to 10 rats orally. The rats were divided into normal, diabetes mellitus (DM), and lipoic acid-treated groups (each group n=10). The eyeballs were harvested 8 weeks after inducing diabetes. The expression of VEGF, erythropoietin, angiopoietin 1 & 2 and NADPH oxidase was examined in the rat retina using immunohistochemistry, RT-PCR, and Western blot. Superoxide formation was examined using dihidroethidium (DHE) stain.
DHE analyses showed increased superoxide formation in the retina of the diabetic group. The superoxide formation was suppressed with lipoic acid treatment. Western blot analysis showed that NADPH oxidase was decreased in the diabetic group and returned to normal level in the lipoic acid treated group. Treatment with lipoic acid blocked hyperglycemia induced increases of VEGF, angiopoietin 2 and erythropoietin shown by immunohistochemistry, RT-PCR, and Western blot analysis.
Superoxide is implicated with expression of angiopoietin and erythropoietin as well as VEGF in diabetic rat retina. Lipoic acid treatment suppressed expression of VEGF, angiopoietin 2 and erythropoietin via blockade of superoxide formation
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