Accumulation of Ages and VEGF Expression in Eyes of SDT Rats

Abstract

Abstract: : Purpose: Advanced glycation end products (AGEs) and vascular endothelial growth factor (VEGF) play important roles in the development of ocular complications in diabetes mellitus. We preliminarily reported a new spontaneously diabetic non–obese Torii rat (SDT rat) with marked hyperglycemia and severe ocular complications (mature cataract, proliferative diabetic retinopathy, and neovascular glaucoma) (Int J Experimental Diab Res 2000). In the present study, we examined by immunohistochemistry the accumulation of AGEs and VEGF expression in the eyes of young SDT rats that did not develop diabetic ocular complications. Methods: Ten eyes were obtained from 35–week–old male SDT rats (n=10). Two rats were not yet diabetic (mean fasting plasma glucose level, 182 mg/dl), and 8 rats were diabetic (mean fasting plasma glucose level, 420 mg/dl). The eyes were fixed and embedded in paraffin and sectioned for immunohistochemical study of VEGF and AGE (pyrraline, pentosidine, carboxy methyl lysine [CML]). Results: In the two eyes without diabetes, staining for VEGF in the ciliary body and CML was observed in 2/2 eyes (100%), and pyrraline and pentosidine in 0/2 eyes (0%); staining for VEGF in the retina and CML was observed in 2/2 eyes (100%), pyrraline in 0/2 eyes (0%), and pentosidine in 1/2 eyes (50%). In the eight eyes with diabetes, staining for VEGF in the ciliary body, pyrraline pentosidine, and CML was seen in 8/8 eyes (100%); staining for VEGF in the retina, pentosidine, and CML was observed in 8/8 eyes (100%), and pyrraline in 6/8 eyes (75%). Conclusions:Accumulation of CML in the ciliary body and retina was observed in rats without diabetes; the CML accumulation stimulates VEGF expression. After diabetes developed, accumulation of other AGEs, pyrraline and pentosidine, was seen, and in combination with CML may cause the severe ocular complications found in SDT rats.

Keywords: diabetic retinopathy • immunohistochemistry • diabetes