Oxidants, antioxidants and mitochondrial function in non‐proliferative diabetic retinopathy (在非增殖性糖尿病视网膜病变中的氧化剂、抗氧化剂以及线粒体功能)

Abstract

BackgroundDiabetic retinopathy (DR) is a preventable cause of visual disability. The aims of the present study were to investigate levels and behavior oxidative stress markers and mitochondrial function in non-proliferative DR (NPDR) and to establish the correlation between the severity of NPDR and markers of oxidative stress and mitochondrial function.MethodsIn a transverse analysis, type 2 diabetes mellitus (T2DM) patients with mild, moderate and severe non-proliferative DR (NPDR) were evaluated for markers of oxidative stress (i.e. products of lipid peroxidation (LPO) and nitric oxide (NO) catabolites) and antioxidant activity (i.e. total antioxidant capacity (TAC), catalase, and glutathione peroxidase (GPx) activity of erythrocytes). Mitochondrial function was also determined as the fluidity of the submitochondrial particles of platelets and the hydrolytic activity of F0/F1-ATPase.ResultsLevels of LPO and NO were significantly increased in T2DM patients with severe NPDR (3.19 ± 0.05 μmol/mL and 45.62 ± 1.27 pmol/mL, respectively; P < 0.007 and P < 0.0001 vs levels in health volunteers, respectively), suggesting the presence of oxidative stress. TAC had significant decrease levels with minimum peak in severe retinopathy with 7.98 ± 0.48 mEq/mL (P < 0.0001). In contrast with TAC, erythrocyte catalase and GPx activity was increased in patients with severe NPDR (139.4 ± 4.4 and 117.13 ± 14.84 U/mg, respectively; P < 0.0001 vs healthy volunteers for both), suggesting an imbalance between oxidants and antioxidants. The fluidity of membrane submitochondrial particles decreased significantly in T2DM patients with mild, moderate, or severe NPDR compared with that in healthy volunteers (P < 0.0001 for all). Furthermore, there was a significant increase in the hydrolytic activity of the F0/F1-ATPase in T2DM patients with mild NPDR (265.07 ± 29.55 nmol/PO4; P < 0.0001 vs healthy volunteers), suggesting increased catabolism.ConclusionsPatients with NPDR exhibit oxidative deregulation with decreased membrane fluidity of submitochondrial particles and increased systemic catabolism (mitochondrial dysfunction) with the potential for generalized systemic damage in T2DM.Significant findings of the study: There were significant increases in lipid peroxidation (LPO) and nitric oxide (NO) from the early stages of non-proliferative diabetic retinopathy (NPDR). Progressive increases in LPO and NO levels are associated with the severity of NPDR, with an imbalance between oxidants, antioxidants and mitochondrial function.What this study adds: Decreased fluidity of membrane submitochondrial particles of platelets and increased F0/F1-ATPase hydrolytic activity are sensitive markers of mitochondrial dysfunction that indicate a catabolic state from the early stages of NPDR.