ABSTRACT
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.
Subject(s)
Animals , Male , Hyperglycemia/complications , Peptidyl-Dipeptidase A/metabolism , Retinal Diseases/etiology , Retinal Diseases/prevention & control , Secondary Prevention/methods , Administration, Oral , Apoptosis , /metabolism , Cell Proliferation/physiology , Cell Survival/physiology , Diabetes Mellitus, Experimental/metabolism , Enzyme Activation , Hyperglycemia/chemically induced , Immunohistochemistry , Peptidyl-Dipeptidase A/drug effects , Rats, Wistar , Retinal Diseases/metabolism , Retinal Ganglion Cells/metabolism , Retinal Ganglion Cells/pathology , Streptozocin , Vascular Endothelial Growth Factor A/metabolism , Xanthones/administration & dosageABSTRACT
To determine the prevalence of retinopathy in hypertensive patients referred to a teaching hospital in Yazd, Iran. This cross-sectional study included 213 hypertensive patients referring to a teaching hospital in Yazd, Iran between November 2004 and June 2005. Data were collected using a questionnaire after an interview and ocular examination. Demographic variables, hypertensive retinopathy, familial history of hypertension, duration of diagnosis, and other hypertension side effects such as cardiac, renal, cerebro-vascular complications were analyzed. The Scheie's staging system was used for retinopathy grading. A total of 213 patients [95 men, 118 women] with high blood pressure aged between 25 and 85 years [mean age of 64.47 +/- 10.66 years] were enrolled in this study, wherein 39.9% of patients suffered from retinopathy. This rate was higher in women [45.6%] than in men [33%]. The positive familial history of hypertension was reported in 47.8% of patients. The prevalence rate of retinopathy in patients suffering from mild hypertension was 25.3%, moderate hypertension was 34.5% and severe hypertension 84.6%. Of the patients with retinopathy, 42.36% had grade I, 20% had grade II and 2.35% had grade III retinopathy. The most common ophthalmoscopic findings were arteriolar narrowing [35.13%], arterio-venous nicking [17.12%] and cotton wool patches [9%]. Positive family history of hypertension and target organs involvement are important risk factors for retinopathy. Early diagnosis and treatment of hypertension to prevent complications is essential