title: Oral carnosine supplementation prevents vascular damage in experimental diabetic retinopathy.
abstract: OBJECTIVE
  Pericyte loss, vasoregression and neuroglial activation are characteristic changes in incipient diabetic retinopathy. In this study, the effect of the antioxidant and antiglycating dipeptide carnosine was studied on the development of experimental diabetic retinopathy.
  
  
  METHODS
  STZ-induced diabetic Wistar rats were orally treated with carnosine (1g/kg body weight/day). Retinal vascular damage was assessed by quantitative morphometry. Retinal protein extracts were analyzed for markers of oxidative stress, AGE-formation, activation of the hexosamine pathway and changes in the expression of Ang-2, VEGF and heat shock proteins Hsp27 and HO-1. Glial cell activation was analyzed using Western blot analysis and immunofluorescence of GFAP expression and retinal neuronal damage was histologically examined.
  
  
  RESULTS
  Oral carnosine treatment prevented retinal vascular damage after 6 months of experimental hyperglycemia. The protection was not caused by ROS- or AGE-inhibition, but associated with a significant induction of Hsp27 in activated glial cells and normalization of increased Ang-2 levels in diabetic retinas. A significant reduction of photoreceptors in retinas of carnosine treated animals was noted.
  
  
  CONCLUSIONS
  Oral carnosine treatment protects retinal capillary cells in experimental diabetic retinopathy, independent of its biochemical function. The vasoprotective effect of carnosine might be mediated by the induction of protective Hsp27 in activated glial cells and normalization of hyperglycemia-induced Ang-2.
authors.affiliation: 5th Medical Department, University Medicine Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Frederick
authors.initials: F
authors.lastname: Pfister
authors.forename: Eva
authors.initials: E
authors.lastname: Riedl
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Franziska
authors.initials: F
authors.lastname: vom Hagen
authors.forename: Martina
authors.initials: M
authors.lastname: Deinzer
authors.forename: Martin Conrad
authors.initials: MC
authors.lastname: Harmsen
authors.forename: Grietje
authors.initials: G
authors.lastname: Molema
authors.forename: Benito
authors.initials: B
authors.lastname: Yard
authors.forename: Yuxi
authors.initials: Y
authors.lastname: Feng
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hammes
mesh_terms: D000284:Administration, Oral; D042702:Angiopoietin-2 / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002336:Carnosine / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors / Q000378:metabolism; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D008297:Male; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D020286:Pericytes / Q000473:pathology; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012171:Retinal Vessels / Q000187:drug effects* / Q000473:pathology; D013311:Streptozocin / Q000633:toxicity; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D042702:Angiopoietin-2; D000975:Antioxidants; D017127:Glycation End Products, Advanced; D055551:HSP27 Heat-Shock Proteins; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; D013311:Streptozocin; D002336:Carnosine; D051547:Heme Oxygenase-1