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

Journal of Diabetes Mellitus 2011年第3期1卷 57-62页

作者： satoru kase Susumu Ishida Narsing Adupa Rao 不详

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.

关键词： Advanced Glycation End Products Choroid Ciliary Body Diabetes Iris Retina

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Phosphorylation of alphaB-crystallin in epiretinal membrane of human proliferative diabetic retinopathy

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International Journal of Ophthalmology(English edition) 2016年第8期9卷 1100-1105页

作者： Yoko Dong Zhenyu Dong satoru kase Ryo Ando Junichi Fukuhara Satoshi Kinoshita Saori Inafuku Yoshiaki Tagawa Erdal Tan Ishizuka Wataru Saito Miyuki Murata Atsuhiro Kanda Kousuke Noda Susumu Ishida Laboratory of Ocular Cell Biology and Visual Science Department of Ophthalmology Hokkaido University Graduate School of Medicine

AIMTo examine phosphorylation of alphaB-crystallin (p-αBC), a vascular endothelial growth factor (VEGF) chaperone, and immunohistochemically investigate relationship between p-αBC, VEGF and phosphorylated p38-mitogen-activated protein kinase (p-p38 MAPK) in the epiretinal membrane of human proliferative diabetic retinopathy (PDR).METHODSEleven epiretinal membranes of PDR surgically excised were included in this study. Two normal retinas were also collected from enucleation tissues due to choroidal melanoma. Paraformaldehyde-fixed, paraffin-embedded tissue sections were processed for immunohistochemistry with anti-p-αBC, VEGF, CD31, and p-p38 MAPK *** for p-αBC was observed in all of the epiretinal membranes examined, where phosphorylation on serine (Ser) 59 showed strongest immunoreactivity in over 70% of the membranes. The immunolocalization of p-αBC was detected in the CD31-positive endothelial cells, and co-localized with VEGF and p-p38 MAPK in PDR membranes. Immunoreactivity for p-αBC, however, was undetectable in endothelial cells of the normal retinas, where p-p38 MAPK immunoreactivity was less marked than PDR *** of αBC, in particular, phosphorylation on Ser59 by p-p38 MAPK may play a potential role as a molecular chaperon for VEGF in the pathogenesis of epiretinal membranes in PDR.

关键词： phosphorylated alphaB-crystallin vascular endothelial growth factor neovascularization proliferative diabetic retinopathy

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