title: Antioxidants and an inhibitor of advanced glycation ameliorate death of retinal microvascular cells in diabetic retinopathy.
abstract: BACKGROUND
  Pericyte ghosts and acellular capillaries are well known as early histological changes resulting from diabetic retinopathy. These histological changes mean that the cell death of retinal microvessels has accelerated. It was reported that apoptosis of retinal microvascular cells (RMCs) was increased in diabetic patients. Therefore, we investigated apoptosis of RMCs in Goto-Kakizaki (GK) rats, a type 2 diabetic model, and involvement with antioxidants (a combination of vitamins C and E) or a novel inhibitor of advanced glycation, OPB-9195.
  
  
  METHODS
  GK rats were treated with the antioxidants combination or OPB-9195 for 36 weeks. We obtained isolated preparations of the vascular network from their retinas by trypsin digestion. Apoptosis of retinal vascular cells was detected with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay.
  
  
  RESULTS
  We found that apoptosis of RMCs was increased in the diabetic GK rats. Furthermore, a combination of vitamins C and E and an advanced glycation end-products inhibitor mostly inhibited this increased apoptosis.
  
  
  CONCLUSIONS
  We concluded that apoptosis of RMCs was a good marker that indicates the progression of diabetic retinopathy in GK rats. Both oxidative stress and the accumulation of advanced glycation end-products appears to promote the apoptosis of retinal microvascular cells, and antioxidants or advanced glycation end-products inhibitors might ameliorate diabetic retinopathy.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan. s-yatoh@yf6.so-net.ne.jp
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yatoh
authors.forename: Masakazu
authors.initials: M
authors.lastname: Mizutani
authors.forename: Tomotaka
authors.initials: T
authors.lastname: Yokoo
authors.forename: Tadahiko
authors.initials: T
authors.lastname: Kozawa
authors.forename: Hirohito
authors.initials: H
authors.lastname: Sone
authors.forename: Hideo
authors.initials: H
authors.lastname: Toyoshima
authors.forename: Seiji
authors.initials: S
authors.lastname: Suzuki
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Shimano
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kawakami
authors.forename: Yukichi
authors.initials: Y
authors.lastname: Okuda
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Yamada
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001205:Ascorbic Acid / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D003930:Diabetic Retinopathy / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D012171:Retinal Vessels / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013830:Thiadiazoles / Q000627:therapeutic use*; D053778:Thiazolidines; D014810:Vitamin E / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D017127:Glycation End Products, Advanced; C105739:OPB 9195; D013830:Thiadiazoles; D053778:Thiazolidines; D014810:Vitamin E; D001205:Ascorbic Acid