Activation of endogenous angiotensin converting enzyme 2 prevents early injuries induced by hyperglycemia in rat retina

作者：Foureaux G; Nogueira B S; Coutinho D C O; Raizada M K; Nogueira J C; Ferreira A J^*

来源：Brazilian Journal of Medical and Biological Research, 2015, 48(12): 1109-1114.

DOI：10.1590/1414-431X20154583

• ACE2 activation
• Angiotensin-(1-7)
• Renin-angiotensin system
• Eyes
• Diabetic retinopathy

Diabetic retinopathy (DR) is a serious complication of diabetes mellitus that may result in blindness. We evaluated the effects of activation of endogenous angiotensin converting enzyme (ACE) 2 on the early stages of DR. Rats were administered an intravenous injection of streptozotocin to induce hyperglycemia. The ACE2 activator 1-[[2-(dimethylamino) ethyl] amino]4-(hydroxymethyl)-7-[[(4- methylphenyl) sulfonyl] oxy]-9H-xanthone 9 (XNT) was administered by daily gavage. The death of retinal ganglion cells (RGC) was evaluated in histological sections, and retinal ACE2, caspase-3, and vascular endothelial growth factor (VEGF) expressions were analyzed by immunohistochemistry. XNT treatment increased ACE2 expression in retinas of hyperglycemic (HG) rats (control: 13.81 +/- 2.71 area%; HG: 14.29 +/- 4.30 area%; HG+ XNT: 26.87 +/- 1.86 area%; P < 0.05). Importantly, ACE2 activation significantly increased the RCG number in comparison with HG animals (control: 553.5 +/- 14.29; HG: 530.8 +/- 10.3 cells; HG+ XNT: 575.3 +/- 16.5 cells; P < 0.05). This effect was accompanied by a reduction in the expression of caspase-3 in RGC of the HG+ XNT group when compared with untreated HG rats (control: 18.74 +/- 1.59; HG: 38.39 +/- 3.39 area%; HG+ XNT: 27.83 +/- 2.80 area%; P < 0.05). Treatment with XNT did not alter the VEGF expression in HG animals (P > 0.05). Altogether, these findings indicate that activation of ACE2 reduced the death of retinal ganglion cells by apoptosis in HG rats.

• 出版日期2015-12