Inhibition of receptor for advanced glycation end products as new promising strategy treatment in diabetic retinopathy

Abstract

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.