Differential profiles of miRNAs, homocystein, vitamin B12/folate levels and oxidative stress parameters in diabetic retinopathy

Abstract

Purpose: Micro RNAs (miRNAs) are essential to the posttranscriptional regulation of gene expression. The miRNAs may target genes involved in oxidative stress, immune response, angiogenesis or apoptosis that in turns, may influence diabetic retinopathy (DR) initiation/progression. We showed that human tears are excellent biosamples for molecular research (Pinazo-Durán et al., Ophthalmic Res 2014; Clin Int Aging 2013). In this study we deal with analyzing current cellular and molecular concepts in DR.

Methods: In this prospective study of cases-controls, 262 participants were distributed into: 1) type 2 diabetics (T2DG; n=160) and 2) healthy controls (CG; n=102) after initial baseline assessmen, interview and ophthalmic examination was followed by collecting blood and tear samples that were processed to biochemical/molecular approaches. Homogeneously, participants from each group were randomly assigned (or not) to a daily intake of one pill containing antioxidants/omega 3 fatty acids (A/w3). Either Wilcoxon or Student’s t-test was used, to assess differences between groups. Parameters associated with/without DR were identified by a cross-validation approach (two subgroups were done via a random number generator). Data were processed using the IBM SPSS (Chicago, IL, USA).

Results: Significantly higher miRNAs expression in tears from the T2DG (9.02 ± 3.08 ng/microL) vs the CG (6.85 ± 3.58 ng/microL) (p=0.022) was found. Glycosylated hemoglobin (p=0.000), homocysteine (Hcys; p=0.032), folate (p=0.050), malondialdehyde (MDA; p=0.030), total antioxidant capacity (TAC; p=0.001) and glutathione (GSH; p=0.031) plasmatic levels significantly changed in the T2DG with/without DR vs the CG. Significantly reduced Hcys (p=0.047) and MDA (p=0.00), and increased folate (p=0.037), TAC (p=0.050) and GSH (p=0.000) plasmatic concentrations were detected at one year of follow-up in the A/w3 supplemented versus the non supplemented diabetics.

Conclusions: Diabetes is associated with oxidative stress that may reflect, in part, a compromised vitamin B12/folate metabolism and hyperhomocysteinemia. These biomarkers and the identification of precise miRNAs in tears could be used as dynamic monitoring factors for detecting the DR initiation or progression. Oral supplementation with A/w3 may exert an additional benefit in diabetics by decreasing lipid peroxidation and enhancing antioxidant defense.