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Chang-Hao Yang, Yu-Hsun Huang, Lu-chun Wang, Chung-May Yang, Muh-Shy Chen; Intervention with Cilostazol Attenuates Retinal Inflammation in a Streptozotocin- Induced Diabetic Animal Model. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5963.
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Diabetic retinopathy (DR) remains the leading cause of blindness in developing countries. New evidence indicates that inflammation and oxidative stress may play a central role in the development of DR. The use of appropriate antioxidants may have potential to inhibit the development of DR. Cilostazol, is a phosphodiesterase 3 (PDE3) inhibitor which shows potent anti-inflammatory and anti-oxidative effects. In the present study, we evaluated the effect of cilostazol in a streptozotocin (STZ) induced diabetic rat model.
Thirty 6 weeks old female Wistar rats were divided into a normal control group (n=10), a STZ-induce diabetic group (n=10) feed with PBS, and a STZ-induce diabetic group (n=10) feed with cilostazol 18 mg/kg/day. Eight weeks later, the eyeball of each rat was enucleated. We performed PCR, western blot analysis, H&E, and immuno histochemical (IHC) staining to assess the expression of ICAM-1, MCP-1 and Fractalkine (FKN) in the retina. The concentrations of ICAM-1, MCP-1 and FKN in the aqueous humor and vitreous cavity were examined by ELISA. The nuclear factor (NF)-ΚB activity was assessed by IHC and electrophoresis mobility shift assay (EMSA). Besides, the oxidative markers of 8-OHdG, nitrotyrosine and acrolein in the retina were measured by IHC.
Cilostazol inhibits the increase of ICAM-1, MCP-1 and FKN mRNA and protein expression in the diabetic retina, as well as the increase of ICAM-1, MCP-1 and FKN contents in the aqueous humor and vitreous cavity. Cilostazol attenuated the enhanced activation of NF-ΚB in diabetic rats by IHC and EMSA findings. The levels of oxidatively modified DNA (8-OHdG), nitrotyrosine and oxidative lipids (acrolein) were also diminished in the cilostazol-treated diabetic group.
Cilostazol reduces inflammatory reactions and oxidative stress in the development of DR. The anti-inflammatory effects of cilostazol is supposed to be mediated by the inhibition of NF-ΚB activity, and the subsequent decrease in inflammatory mediators such as ICAM-1, MCP-1 and FKN expression in the retina. Cilostazol may be clinically applied in the treatment of diabetic patients to avoid visual loss due to DR.
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