Role of the receptor for advanced glycation endproducts (RAGE) in retinal vasodegenerative pathology during diabetes in mice

2015/02/17 by Carmel McVicar, Carmel M. McVicar, Micheal Ward +13 · 81 citations
Biochemistry, Genetics and Molecular Biology · Chemistry · Medicine · #Acute Kidney Injury Research #Advanced Glycation End Products research #Biology #Chemistry #Diabetes mellitus #Diabetic retinopathy #Endocrinology #Endothelial stem cell #Glycation #Internal medicine #Leukostasis #Medicine #Methylglyoxal #Ophthalmology #Pericyte #Rage (emotion) #Retina #Retinal #Retinal Diseases and Treatments #Retinopathy #Streptozotocin

paper · pdf · doi:10.1007/s00125-015-3523-x

published in Diabetologia 58(5), 1129-1137 (Springer Science+Business Media)

openalex publication_date 2015/02/17 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01

Abstract

AIMS/HYPOTHESIS: The receptor for AGEs (RAGE) is linked to proinflammatory pathology in a range of tissues. The objective of this study was to assess the potential modulatory role of RAGE in diabetic retinopathy. METHODS: Diabetes was induced in wild-type (WT) and Rage (-/-) mice (also known as Ager (-/-) mice) using streptozotocin while non-diabetic control mice received saline. For all groups, blood glucose, HbA1c and retinal levels of methylglyoxal (MG) were evaluated up to 24 weeks post diabetes induction. After mice were killed, retinal glia and microglial activation, vasopermeability, leucostasis and degenerative microvasculature changes were determined. RESULTS: Retinal expression of RAGE in WT diabetic mice was increased after 12 weeks (p < 0.01) but not after 24 weeks. Rage (-/-) mice showed comparable diabetes but accumulated less MG and this corresponded to enhanced activity of the MG-detoxifying enzyme glyoxalase I in their retina when compared with WT mice. Diabetic Rage (-/-) mice showed significantly less vasopermeability, leucostasis and microglial activation (p < 0.05-0.001). Rage (-/-) mice were also protected against diabetes-related retinal acellular capillary formation (p < 0.001) but not against pericyte loss. CONCLUSIONS/INTERPRETATION: Rage (-/-) in diabetic mice is protective against many retinopathic lesions, especially those related to innate immune responses. Inhibition of RAGE could be a therapeutic option to prevent diabetic retinopathy.

Citations

• Protection against methylglyoxal-derived AGEs by regulation of glyoxalase 1 prevents retinal neuroglial and vasodegenerative pathology
• Microglial Activation in Human Diabetic Retinopathy

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