Diabetes-induced oxidative stress in the vitreous humor

Zsuzsanna Géhl,Edina Bakondi,Miklós D Resch,Csaba Hegedűs,Katalin Kovács,Petra Lakatos,Antal Szabó,Zoltán Nagy,László Virág

doi:10.1016/j.redox.2016.07.003

Abstract

PurposeDiabetes is accompanied by fundamental rearrangements in redox homeostasis. Hyperglycemia triggers the production of reactive oxygen and nitrogen species which contributes to tissue damage in various target organs. Proliferative diabetic retinopathy (PDR) is a common manifestation of diabetic complications but information on the possible role of reactive intermediates in this condition with special regard to the involvement of the vitreous in PDR-associated redox alterations is scarce.The aim of the study was to determine key parameters of redox homeostasis [advanced glycation endproducts (AGE); protein carbonyl and glutathione (GSH)] content in the vitreous in PDR patients. MethodsThe study population involved 10 diabetic patients undergoing surgery for complications of proliferative diabetic retinopathy and 8 control (non-diabetic) patients who were undergoing surgery for epiretinal membranes. Vitreal fluids were assayed for the above biochemical parameters. ResultsWe found elevated levels of AGE in the vitreous of PDR patients (812.10 vs 491.69ng AGE/mg protein). Extent of protein carbonylation was also higher in the samples of diabetic patients (2.08 vs 0.67A/100μg protein). The GSH content also increased in the vitreous of PDR patients as compared to the control group (4.54 vs 2.35μmol/μg protein), respectively. ConclusionThe study demonstrates that diabetes-associated redox alterations also reach the vitreous with the most prominent changes being increased protein carbonylation and increased antioxidant levels.

Highlights

Diabetes is one of the most prominent diseases in the world and in recent decades its incidence reached “epidemic” proportions
While the efficient treatment of the disease itself especially that of insulin resistance in type 2 diabetes cannot be considered as a solved medical problem, it is the management of diabetic complications that truly represents an unmet medical need
Advanced Glycation End Products (AGE) are stable endproducts formed in a non-enzyme catalyzed reaction between reducing sugars such as glucose and amino groups of proteins

Summary

Introduction

Diabetes is one of the most prominent diseases in the world and in recent decades its incidence reached “epidemic” proportions. While the efficient treatment of the disease itself especially that of insulin resistance in type 2 diabetes cannot be considered as a solved medical problem, it is the management of diabetic complications (e.g. vasculopathy, neuropathy, nephropathy) that truly represents an unmet medical need. The eye is an important target organ often affected by diabetic complications with diabetic n Corresponding author at: Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. Retinopathy being the leading cause of blindness in the developed countries [3]. In 5–10% of diabetes patients proliferative diabetic retinopathy (PDR) develops [4] affecting mostly type I diabetics. PDR is one of the most severe diabetic complications [5] characterized by abnormally proliferating retinal blood vessels, neovascularization and cell proliferation [6]. It often leads to vitreal bleedings and tractional retinal detachment culminating in severe deterioration of vision [7]

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