scholarly journals Involvement of Advanced Glycation End Products in the Pathogenesis of Diabetic Retinopathy

2018 ◽  
Vol 48 (2) ◽  
pp. 705-717 ◽  
Author(s):  
Jing Xu ◽  
Lin-Jiang Chen ◽  
Jian Yu ◽  
Han-Jing Wang ◽  
Fan Zhang ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Advanced Glycation End Products ◽  
Intracellular Signaling ◽  
Vascular Inflammation ◽  
Advanced Glycation ◽  
Blood Retinal Barrier ◽  
Glycation End Products ◽  
End Products ◽  
And Function ◽  
Medical Burden

Diabetic retinopathy (DR) is a common and devastating microvascular complication of diabetes and a major cause of acquired blindness in young adults. Advanced glycation end products (AGEs) accumulated under hyperglycemic conditions are thought to play an important role in the pathogenesis of DR. AGEs can exert their deleterious effects by acting directly to induce aberrant crosslinking of extracellular matrix proteins, to increase vascular stiffness, altering vascular structure and function. Moreover, AGEs binding to the receptor for AGEs (RAGE) evokes intensive intracellular signaling cascades that leading to endothelial dysfunction, elaboration of key proinflammatory cytokines and proangiogenic factors, mediating pericyte apoptosis, vascular inflammation and angiogenesis, as well as breakdown of the inner blood-retinal barrier (BRB), the end result of all these events is damage to the neural and vascular components of the retina. Elucidation of AGE-induced mechanisms will help in the understanding of the complex cellular and molecular pathogenesis associated with DR. Novel anti-AGEs agents or AGE crosslink “breakers” are being investigated, it is hoped that in next few years, some of these promising therapies will be successfully applied in clinical context, aiming to reduce the major economical and medical burden caused by DR.

scholarly journals Advanced Glycation End Products: Formation, Role in Diabetic Complications, and Potential in Clinical Applications

2020 ◽  
Author(s):  
Rujman Khan ◽  
Xin Yee Ooi ◽  
Matthew Parvus ◽  
Laura Valdez ◽  
Andrew Tsin
Keyword(s):  
Diabetic Retinopathy ◽  
Advanced Glycation End Products ◽  
Diabetic Complications ◽  
Tanshinone Iia ◽  
Future Research ◽  
Advanced Glycation ◽  
Reactive Aldehydes ◽  
Glycation End Products ◽  
End Products ◽  
Lysine Residues

Hyperglycemic conditions and disruptions to glucose-regulating pathways lead to increased formation of highly reactive aldehydes, methylglyoxal and glyoxal, which react with certain arginine and lysine residues in proteins to form advanced glycation end products (AGEs). These AGEs damage the integrity of the retinal vasculature predominantly through two mechanisms: non-receptor-mediated damage, which pertains to the interaction with extracellular matrix and its functional properties, and receptor-mediated damage through AGE interactions with their receptors (RAGE) on pericytes and Muller cells. Damage occurring between AGE and RAGE potentially generates reactive oxygen species, inflammatory cytokines, and growth factors. Both mechanisms result in increased permeability of endothelial tight junctions, and this increased permeability can lead to leaking and eventually ischemia. Once this ischemia becomes significant, neovascularization can occur, the hallmark of proliferative diabetic retinopathy. Current pharmaceutical studies have shown the potential of AGE inhibitors, such as aminoguanidine, in decreasing AGE production, thus minimizing its effects in hyperglycemic conditions. Other pharmaceutical interventions, such as Tanshinone IIA, aim to protect cells from the impacts of AGEs. Future research will not only continue to understand the properties of AGEs and their effects on diabetes and diabetic complications like diabetic retinopathy but will also explore how they impact other diseases.

scholarly journals The Modern Western Diet Rich in Advanced Glycation End-Products (AGEs): An Overview of Its Impact on Obesity and Early Progression of Renal Pathology

Nutrients ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1748 ◽  
Author(s):  
Arianna Bettiga ◽  
Francesco Fiorio ◽  
Federico Di Marco ◽  
Francesco Trevisani ◽  
Annalisa Romani ◽  
...  
Keyword(s):  
Chronic Diseases ◽  
Advanced Glycation End Products ◽  
Cell Function ◽  
Advanced Glycation ◽  
Covalent Bonds ◽  
Physiological Processes ◽  
Glycation End Products ◽  
End Products ◽  
And Function

Advanced glycation end-products (AGEs) are an assorted group of molecules formed through covalent bonds between a reduced sugar and a free amino group of proteins, lipids, and nucleic acids. Glycation alters their structure and function, leading to impaired cell function. They can be originated by physiological processes, when not counterbalanced by detoxification mechanisms, or derive from exogenous sources such as food, cigarette smoke, and air pollution. Their accumulation increases inflammation and oxidative stress through the activation of various mechanisms mainly triggered by binding to their receptors (RAGE). So far, the pathogenic role of AGEs has been evidenced in inflammatory and chronic diseases such as chronic kidney disease, cardiovascular disease, and diabetic nephropathy. This review focuses on the AGE-induced kidney damage, by describing the molecular players involved and investigating its link to the excess of body weight and visceral fat, hallmarks of obesity. Research regarding interventions to reduce AGE accumulation has been of great interest and a nutraceutical approach that would help fighting chronic diseases could be a very useful tool for patients’ everyday lives.

Advanced Glycation End Products Modulate the Maturation and Function of Peripheral Blood Dendritic Cells

Diabetes ◽  
2004 ◽  
Vol 53 (6) ◽  
pp. 1452-1458 ◽  
Author(s):  
C. L. Price ◽  
P. S. Sharp ◽  
M. E. North ◽  
S. J. Rainbow ◽  
S. C. Knight
Keyword(s):  
Dendritic Cells ◽  
Advanced Glycation End Products ◽  
Peripheral Blood ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
And Function

scholarly journals Association of the Receptor for Advanced Glycation End Products Gene Polymorphisms and Circulating RAGE Levels with Diabetic Retinopathy in the Chinese Population

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Li Yang ◽  
Qunhong Wu ◽  
Yuan Li ◽  
Xiaohong Fan ◽  
Yanhua Hao ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Advanced Glycation End Products ◽  
Chinese Population ◽  
Genetic Interaction ◽  
Interaction Model ◽  
Serum Levels ◽  
Advanced Glycation ◽  
Soluble Rage ◽  
Glycation End Products ◽  
End Products

Objectives. This study investigated the association between polymorphisms in the receptor for advanced glycation end products (RAGE) gene and the susceptibility to diabetic retinopathy (DR) in a Chinese population and identified a correlation between serum-soluble RAGE (sRAGE) levels and DR risk.Materials and Methods. We enrolled 1040 patients with type 2 diabetes mellitus: 372 patients with DR and 668 without retinopathy (NDR). All polymorphisms were genotyped by time-of-flight mass spectrometry. Serum levels of sRAGE were assayed by enzyme-linked immunosorbent assays. The interaction of SNPs was analyzed by multifactor dimensionality reduction (MDR).Results. The frequency of the SS genotype for the G82S polymorphism was 12.4% in the DR group and 6.6% in the NDR group; this difference was significant. G82S was associated with sRAGE levels. Specifically, after adjustments for age, sex, duration, and glucose metabolism, serum sRAGE levels were significantly higher in DR subjects with the S/S genotype than in NDR subjects in general. In the DR group, subjects with the G/S genotype had lower sRAGE levels than subjects with the G/G or S/S genotype (P<0.01). The best multilocus genetic interaction model was assessed using the MDR method; 2184A/G, 1704G/T, G82S, and −429T/C were identified.Conclusions. The findings suggest that the G82S polymorphism in theRAGEgene is associated with DR risk, and G82S was associated with circulating levels of sRAGE. The mechanism by which G82S polymorphism modulates the sRAGE levels remains to be elucidated.

scholarly journals Autophagy Inhibits the Accumulation of Advanced Glycation End Products by Promoting Lysosomal Biogenesis and Function in the Kidney Proximal Tubules

Diabetes ◽  
2017 ◽  
Vol 66 (5) ◽  
pp. 1359-1372 ◽  
Author(s):  
Atsushi Takahashi ◽  
Yoshitsugu Takabatake ◽  
Tomonori Kimura ◽  
Ikuko Maejima ◽  
Tomoko Namba ◽  
...  
Keyword(s):  
Advanced Glycation End Products ◽  
Proximal Tubules ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
And Function ◽  
Kidney Proximal Tubules
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