RESEARCH ARTICLE


Accumulation of AGEs and VEGF in Eyes of SDT Rats



Fumihiko Toyoda*, 1, Akihiro Kakehashi1, Kana Hashimoto1, Nozomi Kinoshita1, Chiho Kanbara1, Hiroko Yamagami1, Hiroyuki Tamemoto Tamemoto2, San-e Ishikawa2, Yoh Dobashi2, Masanobu Kawakami2, Yasunori Kanazawa3
1 Department of Ophthalmology, Jichi Medical University, Saitama Medical Center; Saitama, Japan
2 Department of Integrated Medicine I, Jichi Medical University, Saitama Medical Center, Saitama, Japan
3 Japanese Diabetes Foundation, Tokyo, Japan.


© Toyoda et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Department of Ophthalmology, Jichi Medical University, Saitama Medical Center, 1-847 Amanuma-cho, Omiya-ku, Saitama, 330-8503, Japan. Tel: +81-48-647- 2111; Fax: +81-648-5188; E-mail: kakeaki@omiya.jichi.ac.jp


Abstract

Background/Aims: The Spontaneously Diabetic Torii (SDT) rat develops advanced diabetic retinopathy (DR). The aim of this study was to identify advanced glycation end products (AGEs) related to vascular endothelial growth factor (VEGF) expression, a cause of DR in SDT rats. Methods: One eye was obtained from six SDT rats (blood glucose, >250 mg/dl) and 10 nondiabetic normal Sprague- Dawley (SD) rats and prepared for immunohistochemical study of VEGF and AGEs (pyrraline, pentosidine, carboxy methyl lysine [CML]). Immunostaining was described as minimal, moderate, and severe. Results: In diabetic rats, for CML, five eyes had severe and one moderate immunostaining. For pyrraline, one eye had moderate and five eyes minimal immunostaining. For pentosidine, one eye had moderate and five eyes minimal immunostaining. For VEGF, three eyes each had moderate and severe immunostaining. In nondiabetic rats, for CML one eye had minimal, seven had moderate, and two had severe immunostaining. For pyrraline, four eyes had moderate and six eyes minimal immunostaining. For pentosidine, 10 eyes had minimal immunostaining. For VEGF, one eye had moderate and nine had minimal immunostaining. The prevalence rates of CML and VEGF were significantly (P<0.05, P<0.001, respectively) greater in diabetic than in nondiabetic rats. The prevalence rates of pyrraline and pentosidine were not significantly (P=0.35, P=0.38) different between diabetic and nondiabetic rats. Conclusion: CML coexists with VEGF and may be involved in the pathogenesis of severe ocular complications in SDT rats.