Anti-RAGE (Receptor Advanced Glycation End products) Antibody Improves Diabetic Retinopathy in Rats via Hypoglycemic and Anti-inflammatory Mechanism
Article Sidebar
-
Anti-RAGE (Receptor Advanced Glycation End products), Diabetic Retinopathy, Glycated Hemoglobin A, Hypoglycemic Agents, Peroxidases, Vascular Endothelial Growth Factor A
Abstract
Background: Receptor advanced glycation end products (RAGE) activation plays an essential role in diabetic retinopathy (DR) progression. This study was aimed to explore the role of anti-RAGE antibodies (RAGE antagonists) in inhibiting DR progression through their hypoglycemic and anti- inflammatory mechanism in diabetic retinopathy induced rats.
Methods: A total of 30 male Wistar rats were randomly divided into five group. The group was consisted of normal control group, DR group without treatment, DR group with anti-RAGE 1 g/kg BW, 10 g/kg BW, and 100 g/kg BW. To assess the diabetic retinopathy, fundus photographs were taken every week using a camera with 16x magnification placed in front of the rat's eyes. Blood glucose was checked by the glucose oxidase-peroxidase method. Retinal TNF-? levels and VEGF were examined using an enzyme-linked immunosorbent assay (ELISA) kit.
Results: The finding of this study showed that anti-RAGE treatment at dose of 10 and 100 g/kg BW, HbA1c levels were significantly higher (p< 0.05) compared to the normal control group but significantly lower (p< 0.05) than in the diabetes group. The mean blood vessel diameter in the DR+anti-RAGE 10 and 100 g/kg BW groups was significantly lower than in the diabetic retinopathy group (p< 0.05). The administration of anti-RAGE 10 and 100 g/kg BW showed the ability to significantly reduce VEGF levels compared to the DR group (p< 0.05).
Conclusions: This study revealed at doses of 10 and 100 g/kg BW, anti-RAGE antibodies improved diabetic retinopathy in Wistar rats through hypoglycemic effects and anti-inflammatory mechanisms.
Full text article
References
Lee R, Wong TY, Sabanayagam C. Epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss. Eye Vis (London). 2015;2:17.
Glovaci D, Fan W, Wong ND. Epidemiology of diabetes mellitus and cardiovascular disease. Curr Cardiol Rep. 2019;21(4):21.
Endris T, Worede A, Asmelash D. Prevalence of diabetes mellitus, prediabetes and its associated factors in Dessie Town, Northeast Ethiopia: A community-based study. Diabetes Metab Syndr Obes. 2019;12:2799-2809.
Fischer R, Maier O. Interrelation of oxidative stress and inflammation in neurodegenerative disease: Role of TNF. Oxid Med Cell Longev. 2015;2015:610813.
Rübsam A, Parikh S, Fort PE. Role of inflammation in diabetic retinopathy. Int J Mol Sci. 2018;19(4):942.
Zhang W, Chen S, Liu ML. Pathogenic roles of microvesicles in diabetic retinopathy. Acta Pharmacol Sin. 2018;39(1):1–11.
Amin R, Ansyori AK, Erna R, Fauzi L. Anti- receptor advanced glycation end products decreases inflammatory pathways in retinopathy diabetics: in vivo study. Open Access Macedonian Journal of Medical Sciences. 2020;8A:414-417.
Snelson M, Lucut E, Coughlan MT. The role of AGE-RAGE as a modulator of gut permeability in diabetes. Int J Mol Sci. 2022;23(3): 1776.
Serban AI, Stanca L, Geicu OI, Dinischiotu A. AGEs-induced IL-6 synthesis precedes RAGE up-regulation in HEK 293 cells: an alternative inflammatory mechanism?. Int J Mol Sci. 2015;16(9):20100-17.
King AJ. The use of animal models in diabetes research. Br J Pharmacol. 2012;166(3):877-94.
Vucetic M, Jensen PK, Jansen EC. Diameter variations of retinal blood vessels during and after treatment with hyperbaric oxygen. Br J Ophthalmol. 2004;88(6):771-5.
NIH (National Institute of Health). Principles of laboratory animal care. Bethesda, MD. National Institute of Health, 1985; 1-96. 13.Chandra S, Sheth J, Anantharaman G, Gopalakrishnan M. Ranibizumab-induced retinal reperfusion and regression of neovascularization in diabetic retinopathy: An angiographic illustration. Am J Ophthalmol Case Rep. 2018;9:41-44.
Cen S, Hsu Y, Lin Y, Huang YC, Chen CJ, Lin WD, et al. Current concepts regarding developmental mechanisms in diabetic retinopathy in Taiwan. Biomedicine (Taipei). 2016;6(2):7.
Eshaq RS, Aldalati AMZ, Alexander JS, Harris NR. Diabetic retinopathy: Breaking the barrier. Pathophysiology. 2017;24(4):229241.
Cheung CY, Ikram MK, Sabanagayam C, Wong TY. Retinal microvasculature as a model to study the manifestations of hypertension. Hypertension. 2012;60:1094-103.
Song P, Yu J, Chan KY, Theodoratou E, Rudan I. Prevalence, risk factors and burden of diabetic retinopathy in China: a systematic review and meta-analysis. J Glob Health. 2018;8(1):010803.
Sasongko MB, Widyaputri F, Agni AN, Wardhana FS, Kotha S, Gupta P, et al. Prevalence of diabetic retinopathy and blindness in Indonesian adults with type 2 diabetes. Am J Ophthalmol. 2017;181:79–87.
Croft M, Siegel RM. Beyond TNF: TNF superfamily cytokines as targets for the treatment of rheumatic diseases. Nat Rev Rheumatol. 2017;13(4):217-233.
Liu L, Zuo Z, Lu S, Liu A, Liu X. Naringin attenuates diabetic retinopathy by inhibiting inflammation, oxidative stress and NF-?B activation in vivo and in vitro. Iran J Basic Med Sci. 2017;20(7):813821.
Feng Y, Gross S, Chatterjee A, Wang Y, Lin J, Hammes HP. Transcription of inflammatory cytokine TNF? is upregulated in retinal angiogenesis under hyperoxia. Cell Physiol Biochem. 2016;39(2):573–83.
Atli H, Onalan E, Yakar B, Duzenci D, Dönder E. Predictive value of inflammatory and hematological data in diabetic and nondiabetic retinopathy. Eur Rev Med Pharmacol Sci. 2022;26(1):76-83.
Ahuja S, Saxena S, Akduman L, Meyer CH, Kruzliak P, Khanna VK. Serum vascular endothelial growth factor is a biomolecular biomarker of severity of diabetic retinopathy. Int J Retina Vitreous. 2019;5:29.
Simo R, Sundstrom JM, Antonetti DA. Ocular anti-VEGF therapy for diabetic retinopathy: the role of VEGF in the pathogenesis of diabetic retinopathy. Diabetes Care.
Authors
Copyright (c) 2023 Tiara Bunga Indiarsih, Ramzi Amin, A.K. Ansyori
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.