Yasunori Segawa a , Yutaka Shirao a , Sho-ichi Yamagishi b , Tomomi Higashide a , Miho Kobayashi c , Kenji Katsuno c , Akira Iyobe c , Hiromu Harada c , Fumiyasu Sato c , Hiroshi Miyata d , Hiroshi Asai a , Akira Nishimura a , Masayuki Takahira a , Tsutomu Souno a , Youji Segawa a , Kazuhiko Maeda a , Kenji Shima e , Akira Mizuno e , Hiroshi Yamamoto b , Kazuo Kawasaki a
05 October 1998
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.