title: Investigation of ocular neovascularization-related genes and oxidative stress in diabetic rat eye tissues after resveratrol treatment.
abstract: Changes in vascular endothelial growth factor (VEGF), angiotensin-converting enzyme (ACE), matrix metalloproteinase (MMP)-9, and endothelial nitric oxide synthase (eNOS) mRNA expression profiles and oxidative stress in the eye tissue microenviroment may have important roles in ocular neovascularization and permeability in proliferative diabetic retinopathy. The present study investigated the effects of resveratrol (RSV) treatment on the mRNA expression profile of VEGF, ACE, MMP-9, and eNOS, which are associated with vascular neovascularization, and glutathione, protein carbonyl, and nitrite-nitrate levels, which are markers of oxidative stress in eyes of diabetic rats. Twenty-four Wistar albino male rats were divided into four groups. After diabetes induction with streptozotocin (10 mg/kg/day) RSV was administered to the RSV and diabetes mellitus (DM) + RSV groups for 4 weeks. The mRNA levels were measured by quantitative real-time polymerase chain reaction assay, and biochemical estimations were determined with spectrophotometric assays in eye homogenates. The mRNA expression levels of VEGF, ACE, and MMP-9 were increased in the DM group compared with the control group, and RSV treatment decreased their mRNA levels. Expression of eNOS mRNA was increased in the RSV and DM groups and decreased in the DM + RSV group. Nitrite-nitrate levels and protein carbonyl content were increased and glutathione levels were decreased in the DM group compared with controls. Consequently, these data suggest that RSV suppressed the expression of eNOS, which is actively involved in the inflammation and healing process in chronic diabetes. Although oxidative stress was increased in eye tissue from diabetic rats, mRNA levels of VEGF, MMP-9, and ACE genes associated with vascular remodeling did not change in diabetic eyes.
authors.affiliation: Department of Medical Biology and Genetics, Gazi University, Ankara, Turkey. atiyeseda@yahoo.com
authors.forename: Atiye Seda
authors.initials: AS
authors.lastname: Yar
authors.forename: Sevda
authors.initials: S
authors.lastname: Menevse
authors.forename: Irem
authors.initials: I
authors.lastname: Dogan
authors.forename: Ebru
authors.initials: E
authors.lastname: Alp
authors.forename: Volkan
authors.initials: V
authors.lastname: Ergin
authors.forename: Ahmet
authors.initials: A
authors.lastname: Cumaoglu
authors.forename: Aysel
authors.initials: A
authors.lastname: Aricioglu
authors.forename: Abdullah
authors.initials: A
authors.lastname: Ekmekci
authors.forename: Adnan
authors.initials: A
authors.lastname: Menevse
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003930:Diabetic Retinopathy / Q000473:pathology; D005123:Eye / Q000187:drug effects / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000473:pathology*; D009566:Nitrates / Q000032:analysis; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D009573:Nitrites / Q000032:analysis; D018384:Oxidative Stress; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage*; D013311:Streptozocin / Q000009:adverse effects / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D009566:Nitrates; D009573:Nitrites; D012333:RNA, Messenger; D013267:Stilbenes; D042461:Vascular Endothelial Growth Factor A; D013311:Streptozocin; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat; D000077185:Resveratrol