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Enalapril alters expression of key growth factors in experimental diabetic retinopathy
Hyun Woong Kim1, Jung Lim Kim, Han Kee Lee
1Department of Ophthalmology, College of Medicine, Inje University, Busan Paik Hospital, Busan, South Korea. maekbak@hanmail.net
Purpose:
Angiogenic factors such as vascular endothelial growth factor (VEGF), erythropoietin, and angiopoietin play important roles in the development of diabetic retinopathy. However, the suppression of a single factor does not inhibit angiogenesis completely. This study simultaneously evaluated the expression of several angiogenic factors in the retinas of diabetes-induced rats and determined the effects of an angiotensin-converting enzyme inhibitor (enalapril) on the expression of angiogenic factors.
Methods:
Diabetes was chemically induced by injecting 14 of 21 Sprague-Dawley rats with streptozotocin. After induction of diabetes, enalapril (10 mg/kg) was administered orally to seven rats. The rats were divided into normal, diabetes mellitus (DM), and enalapril-treated groups (each group, n = 7). The eyeballs were removed at 8 weeks after the induction of diabetes, and the retinal expression of VEGF, the signal transducer and activator of transcription (STAT)3/5, erythropoietin, and angiopoietin were examined using immunohistochemistry, RT-PCR, and Western blotting.
Results:
RT-PCR revealed that the expression of VEGF, VEGF receptors, STAT3, erythropoietin, erythropoietin receptor, STAT5, angiopoietin 2, and Tie2 mRNA increased in the DM group, whereas angiopoietin 1 expression decreased. The enalapril-treated group showed no increase in mRNA expression of angiogenic factors. Immunohistochemical staining and Western blotting showed that the expression of VEGF, STAT3, and erythropoietin receptor proteins increased in the DM group but not in the enalapril-treated group. Erythropoietin and angiopoietin proteins were not detected by immunohistochemical staining or Western blotting. STAT5 protein expression was detected only in the DM group using immunohistochemical staining and Western blotting. The mRNA expression of the angiogenic factors VEGF, erythropoietin, and angiopoietin 2 increased in the DM group but not in the enalapril-treated group. In contrast, angiopoietin 1 mRNA expression decreased in the DM group.
Conclusions:
Enalapril treatment prevented increased angiogenic factor levels in the retinas of experimentally induced diabetic rats.
Insights
Enalapril treatment prevented increased levels of key angiogenic factors, such as VEGF and erythropoietin, in the retinas of diabetic rats. This suggests a potential therapeutic benefit for diabetic retinopathy.
Area of Science:
- Ophthalmology
- Diabetology
- Molecular Biology
Background:
- Diabetic retinopathy (DR) involves complex angiogenesis driven by multiple factors.
- Single-factor suppression is insufficient to inhibit DR-related angiogenesis.
- Understanding the interplay of angiogenic factors is crucial for DR treatment.
Purpose of the Study:
- To evaluate the expression of multiple angiogenic factors in diabetic rat retinas.
- To determine the effect of enalapril, an ACE inhibitor, on these factors.
- To investigate enalapril's potential in managing diabetic retinopathy.
Main Methods:
- Diabetes induced in Sprague-Dawley rats using streptozotocin.
- Enalapril administered to a subset of diabetic rats.
- Retinal expression of VEGF, STAT3/5, erythropoietin, and angiopoietins analyzed via immunohistochemistry, RT-PCR, and Western blotting.
Main Results:
- Diabetes increased retinal mRNA and protein expression of VEGF, STAT3, erythropoietin receptor, and STAT5.
- Angiopoietin 2 mRNA and Tie2 mRNA also increased, while angiopoietin 1 mRNA decreased in diabetic rats.
- Enalapril treatment normalized the expression of these angiogenic factors and their receptors.
Conclusions:
- Enalapril effectively prevented the upregulation of multiple angiogenic factors in diabetic rat retinas.
- This study highlights enalapril's potential as a therapeutic agent for diabetic retinopathy.
- Targeting multiple angiogenic pathways simultaneously may be key in treating DR.
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