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Antioxidants and an inhibitor of advanced glycation ameliorate death of retinal microvascular cells in diabetic retinopathy
Author(s) -
Yatoh Shigeru,
Mizutani Masakazu,
Yokoo Tomotaka,
Kozawa Tadahiko,
Sone Hirohito,
Toyoshima Hideo,
Suzuki Seiji,
Shimano Hitoshi,
Kawakami Yasushi,
Okuda Yukichi,
Yamada Nobuhiro
Publication year - 2005
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.562
Subject(s) - glycation , diabetic retinopathy , pericyte , retinal , tunel assay , apoptosis , oxidative stress , diabetes mellitus , terminal deoxynucleotidyl transferase , programmed cell death , medicine , endocrinology , pharmacology , chemistry , endothelial stem cell , biochemistry , ophthalmology , in vitro
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. Copyright © 2005 John Wiley & Sons, Ltd.