Abstract
Purpose: :
: 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.
Methods: :
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.
Results: :
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.
Conclusions: :
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.
Keywords: vascular endothelial growth factor • diabetic retinopathy