Antioxidants and an inhibitor of advanced glycation ameliorate death of retinal microvascular cells in diabetic retinopathy.
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.
Yatoh
Shigeru
S
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
Mizutani
Masakazu
M
Yokoo
Tomotaka
T
Kozawa
Tadahiko
T
Sone
Hirohito
H
Toyoshima
Hideo
H
Suzuki
Seiji
S
Shimano
Hitoshi
H
Kawakami
Yasushi
Y
Okuda
Yukichi
Y
Yamada
Nobuhiro
N
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
D000975:Antioxidants; D017127:Glycation End Products, Advanced; C105739:OPB 9195; D013830:Thiadiazoles; D053778:Thiazolidines; D014810:Vitamin E; D001205:Ascorbic Acid