Immunolocalization of advanced glycation end products in human diabetic eyes: an immunohistochemical study

Abstract

Background: Advanced glycation end-products (AGEs) play a critical role in the pathology of diabetic complications. The aim of this study is to examine the immunolocalization of advanced glycation end products (AGE) and receptor for AGE (RAGE) in human diabetic and non-diabetic donor eyes using immunohistochemistry. Materials and Methods: Eight globes were obtained from human postmortem donors: six diabetic donors and two non-diabetic. Formalin-fixed, paraffin-embedded tissue sections were subjected to immunohistochemistry with anti-AGE, and RAGE antibodies. Results: In eyes from diabetic donors, the blood vessels of the iris and choroid had relatively thickened walls. The ciliary body showed decreased capillaries with hyalinization in the stroma. Neovascularization or proliferative changes were not observed in the tissues. Immunoreactivity for AGE was highly detected in the stroma and blood vessels of the iris, ciliary body, choriocapillaris, choroidal large vessels, and central retinal artery/vein. Immunoreactivity was also detected in the retina, corneal endothelium, and lens. RAGE immunoreactivity was weakly detected in choroidal vessels and Bruch’s membrane. In eyes from non-diabetic donors, AGE was weakly detected in the iris, ciliary body stroma, and choriocapillaris, but RAGE was hardly detected. Conclusion: AGE is highly accumulated in vascularized intraocular tissues of diabetic eyes, suggesting that AGE accumulation may play an important role in the pathogenesis of diabetic vasculopathy. This study indicates that inhibition of AGE formation may be an important therapeutic strategy for suppressing the progression of diabetic ocular complications.