title: Activation of endogenous angiotensin converting enzyme 2 prevents early injuries induced by hyperglycemia in rat retina.
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.
authors.affiliation: Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil.
authors.forename: G
authors.initials: G
authors.lastname: Foureaux
authors.affiliation: Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil.
authors.forename: B S
authors.initials: BS
authors.lastname: Nogueira
authors.affiliation: Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil.
authors.forename: D C O
authors.initials: DC
authors.lastname: Coutinho
authors.affiliation: Department of Physiology and Functional Genomics, McKnight Brain Institute, University of Florida, Gainesville, FL, USA.
authors.forename: M K
authors.initials: MK
authors.lastname: Raizada
authors.affiliation: Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil.
authors.forename: J C
authors.initials: JC
authors.lastname: Nogueira
authors.affiliation: Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil.
authors.forename: A J
authors.initials: AJ
authors.lastname: Ferreira
mesh_terms: D000284:Administration, Oral; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D004789:Enzyme Activation; D006943:Hyperglycemia / Q000139:chemically induced / Q000150:complications*; D007150:Immunohistochemistry; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000187:drug effects / Q000378:metabolism*; D017208:Rats, Wistar; D012164:Retinal Diseases / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control*; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology; D055502:Secondary Prevention / Q000379:methods*; D013311:Streptozocin; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D044004:Xanthones / Q000008:administration & dosage
chemical_list: C541435:1-((2-dimethylamino)ethylamino)-4-(hydroxymethyl)-7-((4-methylphenyl)sulfonyloxy)-9H-xanthene-9-one; D042461:Vascular Endothelial Growth Factor A; D044004:Xanthones; D013311:Streptozocin; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2; D053148:Caspase 3