Upregulation of retinal vascular endothelial growth factor mRNAs in spontaneously diabetic rats without ophthalmoscopic retinopathy - A possible participation of advanced glycation end products in the development of the early phase of diabetic retinopathy

被引:60
作者
Segawa, Y
Shirao, Y
Yamagishi, S
Higashide, T
Kobayashi, M
Katsuno, K
Iyobe, A
Harada, H
Sato, F
Miyata, H
Asai, H
Nishimura, A
Takahira, M
Souno, T
Segawa, Y
Maeda, K
Shima, K
Mizuno, A
Yamamoto, H
Kawasaki, K [1 ]
机构
[1] Kanazawa Univ, Sch Med, Dept Ophthalmol, Kanazawa, Ishikawa 9208641, Japan
[2] Kanazawa Univ, Sch Med, Dept Biochem, Kanazawa, Ishikawa 9208641, Japan
[3] Kissei Pharmaceut Co, Discovery Res Lab 3, Matsumoto, Nagano, Japan
[4] Kissei Pharmaceut Co, R&D, Planning Discovery Res, Matsumoto, Nagano, Japan
[5] Univ Tokushima, Sch Med, Dept Lab Med, Tokushima 770, Japan
关键词
vascular endothelial growth factor; advanced glycation end products; spontaneously diabetic rats; reverse transcription polymerase chain reaction; electroretinogram; oscillatory potentials;
D O I
10.1159/000055493
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
Vascular endothelial growth factor (VEGF) has recently been shown to be involved in the pathogenesis of proliferative diabetic retinopathy. However, its involvement in the development of the early phase of diabetic retinopathy is not fully understood. In this study we investigated the retinal VEGF mRNA level in spontaneously diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats, a model of non-insulin-dependent diabetes, without overt retinopathy, using quantitative reverse-transcription polymerase chain reaction. The retinal VEGF mRNA level was 2.2 times higher (p < 0.0005) in OLETF rats than in control rats at the age of 60 weeks. Moreover, their retinal mRNA level was positively correlated with serum concentration of advanced glycation end products (AGEs) but not to serum glucose concentration. Furthermore, the peak latency of the oscillatory potentials in the electroretinogram, one of the most sensitive markers for the early phase of diabetic retinopathy, was significantly prolonged in OLETF rats (p < 0.05), being also correlated with the serum AGE concentration. The results thus suggest that AGEs, which are formed acceleratedly in diabetic conditions, are involved in the development of the early phase of diabetic retinopathy probably through the induction of retinal VEGF mRNAs.
引用
收藏
页码:333 / 339
页数:7
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