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H. Kim, I. Chung, H. Lee; The Effect of Enalapril on Expressions of Angiogenic Factors in Diabetes-Induced Rat Retina. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3878. doi: https://doi.org/.
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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. However, the suppression of a single factor does not inhibit angiogenesis. This study evaluated the expression of several angiogenic factors simultaneously in the experimental diabetes-induced rat retina and the effect of an angiotensin converting enzyme inhibitor (enalapril) on the angiogenic factors.
Diabetes was induced chemically by injecting 14 of 21 Sprague-Dawley rats with streptozotocin. After inducing diabetes, enalapril (10 mg/kg) was administered to 7 rats orally. The rats were divided into normal, diabetes mellitus (DM), and enalapril-treated groups (each group n=7). The eyeballs were removed 8 weeks after inducing diabetes. The expression of VEGF, STAT3 & 5, erythropoietin, and angiopoietin was examined in the rat retina using immunohistochemistry, RT-PCR, and Western blotting.
Using RT-PCR, in the DM group, the expression of VEGF, VEGF receptors, STAT3, erythropoietin, erythropoietin receptor, STAT5, angiopoietin 2, and Tie2 mRNA was elevated, while angiopoietin 1 expression was decreased. This elevated expression of angiogenic factor mRNA was normalized in the enalapril-treated group. The expression of VEGF, STAT3, and erythropoietin receptor was increased in the DM group using immunohistochemical staining and Western blotting and normalized in the enalapril-treated group. Erythropoietin and angiopoietin were not detected on immunohistochemical staining or Western blotting. STAT5 was detected only in the diabetic group using immunohistochemical staining and Western blotting.
The expression of the angiogenic factors VEGF, erythropoietin, and angiopoietin was elevated in the diabetic group and normalized in the enalapril-treated group. The expression of angiopoietin 1 showed the opposite pattern. The administration of enalapril reduced the effect of angiogenic factors in the experimental diabetic rat retina.
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