Antioxidants and an inhibitor of advanced glycation ameliorate death of retinal microvascular cells in diabetic retinopathy

Diabetes Metab Res Rev. 2006 Jan-Feb;22(1):38-45. doi: 10.1002/dmrr.562.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / therapeutic use*
  • Apoptosis / drug effects*
  • Ascorbic Acid / therapeutic use
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology
  • Diabetes Mellitus, Type 2 / prevention & control*
  • Diabetic Retinopathy / metabolism
  • Diabetic Retinopathy / pathology
  • Diabetic Retinopathy / prevention & control*
  • Disease Models, Animal
  • Glycation End Products, Advanced / antagonists & inhibitors*
  • Glycation End Products, Advanced / metabolism
  • In Situ Nick-End Labeling
  • Male
  • Oxidative Stress
  • Rats
  • Rats, Wistar
  • Retinal Vessels / drug effects*
  • Retinal Vessels / metabolism
  • Retinal Vessels / pathology
  • Thiadiazoles / therapeutic use*
  • Thiazolidines
  • Vitamin E / therapeutic use

Substances

  • Antioxidants
  • Glycation End Products, Advanced
  • OPB 9195
  • Thiadiazoles
  • Thiazolidines
  • Vitamin E
  • Ascorbic Acid