scholarly journals Inhibition of Receptor for Advanced Glycation End Products as New Promising Strategy Treatment in Diabetic Retinopathy

2019 ◽  
Vol 7 (23) ◽  
pp. 3921-3924 ◽  
Author(s):  
Irsan Saleh ◽  
Ziske Maritska ◽  
Nita Parisa ◽  
Rachmat Hidayat
Keyword(s):  
Diabetic Retinopathy ◽  
Growth Factor ◽  
Advanced Glycation End Products ◽  
Negative Control ◽  
Advanced Glycation ◽  
Vegf Expression ◽  
White Rats ◽  
Glycation End Products ◽  
End Products

BACKGROUND: Extensive intracellular and extracellular formation of advanced glycation end-products (AGEs) is considered a causative factor for vascular injury triggered by hyperglycemia in diabetes. The hyperglycemia will cause accumulation of AGEs, damage to pericytes, nerve growth factor (NGF), glial acid fibrillary protein (GFAP) and increase in vascular endothelial growth factor (VEGF). AIM: This study aimed to assess the efficacy of RAGE inhibition in suppressing the development and progression of diabetic retinopathy through modulation of the inflammatory pathway involving NGF, GFAP, and VEGF. METHODS: The design was in vivo experimental study. Thirty white rats were induced with Alloxan monohydrate. Rats were divided into 5 groups, normal, negative control, groups with an anti-RAGE dose of 1 μg/uL, the dose of 10 μg/uL and 100 μg/uL. After 4 weeks of treatment, HbA1c, NGF, and GFAP levels were measured using ELISA. Quantification of VEGF expression was done using the ImageJ® application. Data was expressed with mean ± SD. Independent T-test with ANOVA and Tukey's post hoc was done. RESULTS: RAGE inhibitors yielded a significant decrease in blood glucose and HbA1c levels. VEGF and RAGE expression were reduced in anti-RAGE groups in various doses. Inhibition of RAGE reduced the damage of retinal pericytes, by reducing GFAP and increasing NGF, and reduced the formation of new blood vessels, by decreasing VEGF expression, in diabetic retinopathy. CONCLUSION: Inhibition of receptor for advanced glycation end-products (RAGE) was effective in suppressing the development and progression of diabetic retinopathy.

scholarly journals Anti-receptor Advanced Glycation End Products Decreases Inflammatory Pathways in Retinopathy Diabetics: In vivo Study

2020 ◽  
Vol 8 (A) ◽  
pp. 414-417
Author(s):  
Ramzi Amin ◽  
A. K. Ansyori ◽  
Riani Erna ◽  
Lilianty Fauzi
Keyword(s):  
Diabetic Retinopathy ◽  
Negative Control ◽  
Control Group ◽  
Advanced Glycation ◽  
Experimental Animals ◽  
Retinal Tissue ◽  
White Rats ◽  
Glycation End Products ◽  
End Products

BACKGROUND: Diabetic retinopathy is an emerging microvascular complication of diabetes mellitus and a causes of blindness in individuals between ages 30 and 70 years, which is characterized by increased proliferation of blood vessels, vascular occlusion, angiogenesis, loss of pericytes from retinal capillaries, microaneurysms, retinal bleeding, increased retinal capillary permeability, thickening of capillary basal membranes, and infarcts that affect the retina, induced to permanent blindness. AIM: This study aimed to find the role of receptor advanced glycation end products (RAGE) inhibition in lowering the vascularization process which causes a decrease in retinal function on diabetic retinopathy. MATERIALS AND METHODS: This research was an in vivo experimental study. A total of 30 male Wistar rats (200 ± 20 g) were obtained from Eureka Research Laboratory (Palembang, Indonesia). Experimental animals were placed in cages under controlled conditions (12 h of light/dark cycles with temperatures of 22 ± 1°C and humidity of 40–60%), fed and drank ad libitum. White rats were induced by diabetes mellitus using alloxan at a dose of 120 mg/kgBW, intraperitoneally, accompanied by drinking 10% glucose solution for 140 days. Furthermore, experimental animals were grouped into five groups (at eight animals per group), Group 1: Normal control, Group 2: Negative control (induced diabetics retinopathy and given intravenous aquadest), Group 3: Given anti-RAGE 1 ng/mL, Group 4: Given anti-RAGE 10 ng/mL, and Group 5: Given anti-RAGE 100 ng/mL. Giving anti-RAGE was done in a single dosage and intravitreal. After the rats were sacrificed by intraperitoneal injection of 10% chloral hydrate, the evacuation of the eye’s retinal tissue was then carried out, fixed in a 4% paraformaldehyde buffer for immunohistochemistry examination of the eye’s retinal tissue. Evaluation of the expression of nuclear factor-κβ (NF-kB) and intercellular adhesion molecule-1 (ICAM-1) used Image J Software so that the percentage of NF-kB and ICAM-1 expression would be obtained. RESULTS: Negative control group showed an increase in NF-kB expression in the retinal tissue of diabetic retinopathy rats. Administration of anti-RAGE showed its potential to suppress NF-kB expression in retinal tissue of diabetic retinopathy white rats as well with an increase of anti-RAGE dose from 1 ng/mL to 100 ng/mL. Activation of NF-kB causes activation of the inflammatory cascade, which is characterized by the production of pro-inflammatory cytokines, one of which is ICAM-1. Giving anti-RAGE could suppress the expression of ICAM-1 along with an increase in anti-RAGE dose. CONCLUSION: Anti-RAGE is able to block the inflammatory process, by inhibiting the expression of NF-kB and ICAM-1 in the retinal tissue of diabetics retinopathy in white rats.

scholarly journals Advanced glycation end products induce immature angiogenesis in in vivo and ex vivo mouse models

2020 ◽  
Vol 318 (3) ◽  
pp. H519-H533 ◽  
Author(s):  
Lixian Chen ◽  
Yun Cui ◽  
Bingyu Li ◽  
Jie Weng ◽  
Weiju Wang ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Advanced Glycation End Products ◽  
Ex Vivo ◽  
Aortic Ring ◽  
Treated Mouse ◽  
Mouse Retina ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products

Proliferative diabetic retinopathy (PDR) is a progressive disease predominantly involving pathological angiogenesis and is characterized by the development of immature, fragile, and easily hemorrhagic new vessels. Advanced glycation end products (AGEs) and the receptor for AGEs (RAGE) play important roles in the progression of diabetic retinopathy. Our previous studies demonstrated that AGEs promoted HUVEC angiogenesis by inducing moesin phosphorylation via RhoA/Rho-associated protein kinase (ROCK) pathway. The aim of this study was to further confirm AGE-induced angiogenesis in vivo and the involvement of RAGE, ROCK, and moesin phosphorylation in this process. We performed the study in an AGE-treated mouse model with various angiogenesis assays in multiple in vivo and ex vivo models. The results demonstrated that AGEs promoted significant neovascularization in whole mount retina and mouse aortic ring of adult and postnatal mice and in Matrigel plug as well, which were consistently accompanied by increased moesin phosphorylation. The increase of AGE-evoked neovascularization and moesin phosphorylation were both attenuated by RAGE knockout or ROCK inhibitor Y27632 administration in mice. We also revealed the pathological characteristics of AGE-promoted angiogenesis by demonstrating the decrease of pericyte coverage and the disarranged endothelial alignment in microvessels. In conclusion, this study provides in vivo evidences that AGEs induce immature angiogenesis by binding to RAGE, activating the RhoA/ROCK signal pathway and inducing moesin phosphorylation. NEW & NOTEWORTHY Advanced glycation end product (AGE)-induced formation of neovessels and phosphorylation of moesin in retina and aortic ring required AGE receptors. AGEs increased neovessels and the phosphorylation of moesin in retina and aortic ring via RhoA/ROCK pathway. AGE-induced immature angiogenesis in AGE-treated mouse retina and aortic ring. The AGE-RAGE axis and moesin could be candidate targets for overcoming relative diseases.

scholarly journals Influence of Dopamine on Fluorescent Advanced Glycation End Products Formation Using Drosophila melanogaster

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 453
Author(s):  
Ana Filošević Vujnović ◽  
Katarina Jović ◽  
Emanuel Pištan ◽  
Rozi Andretić Waldowski
Keyword(s):  
Drosophila Melanogaster ◽  
Advanced Glycation End Products ◽  
Model Organism ◽  
Covalent Modification ◽  
Advanced Glycation ◽  
Biomarkers Of Aging ◽  
Glycation End Products ◽  
End Products

Non-enzymatic glycation and covalent modification of proteins leads to Advanced Glycation End products (AGEs). AGEs are biomarkers of aging and neurodegenerative disease, and can be induced by impaired neuronal signaling. The objective of this study was to investigate if manipulation of dopamine (DA) in vitro using the model protein, bovine serum albumin (BSA), and in vivo using the model organism Drosophila melanogaster, influences fluorescent AGEs (fAGEs) formation as an indicator of dopamine-induced oxidation events. DA inhibited fAGEs-BSA synthesis in vitro, suggesting an anti-oxidative effect, which was not observed when flies were fed DA. Feeding flies cocaine and methamphetamine led to increased fAGEs formation. Mutants lacking the dopaminergic transporter or the D1-type showed further elevation of fAGEs accumulation, indicating that the long-term perturbation in DA function leads to higher production of fAGEs. To confirm that DA has oxidative properties in vivo, we fed flies antioxidant quercetin (QUE) together with methamphetamine. QUE significantly decreased methamphetamine-induced fAGEs formation suggesting that the perturbation of DA function in vivo leads to increased oxidation. These findings present arguments for the use of fAGEs as a biomarker of DA-associated neurodegenerative changes and for assessment of antioxidant interventions such as QUE treatment.

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