Clinical and Molecular-Genetic Insights into the Role of Oxidative Stress in Diabetic Retinopathy: Antioxidant Strategies and Future Avenues

Abstract

Reactive oxygen species (ROS) overproduction and ROS-signaling pathways activation attack the eyes. We evaluated the oxidative stress (OS) and the effects of a daily, core nutritional supplement regimen containing antioxidants and omega 3 fatty acids (A/ω3) in type 2 diabetics (T2DM). A case-control study was carried out in 480 participants [287 T2DM patients with (+)/without (−) diabetic retinopathy (DR) and 193 healthy controls (CG)], randomly assigned to a daily pill of A/ω3. Periodic evaluation through 38 months allowed to outline patient characteristics, DR features, and classic/OS blood parameters. Statistics were performed by the SPSS 24.0 program. Diabetics displayed significantly higher circulating pro-oxidants (p = 0.001) and lower antioxidants (p = 0.0001) than the controls. Significantly higher plasma malondialdehyde/thiobarbituric acid reactive substances (MDA/TBARS; p = 0.006) and lower plasma total antioxidant capacity (TAC; p = 0.042) and vitamin C (0.020) was found in T2DM + DR versus T2DM-DR. The differential expression profile of solute carrier family 23 member 2 (SLC23A2) gene was seen in diabetics versus the CG (p = 0.001), and in T2DM + DR versus T2DM − DR (p < 0.05). The A/ω3 regime significantly reduced the pro-oxidants (p < 0.05) and augmented the antioxidants (p < 0.05). This follow-up study supports that a regular A/ω3 supplementation reduces the oxidative load and may serve as a dietary prophylaxis/adjunctive intervention for patients at risk of diabetic blindness.

Role of Oral Antioxidant Supplementation in the Current Management of Diabetic Retinopathy

“…After reviewing the abstracts of the 125 initial results by two different researchers, 15 studies were finally included: one case-control observational study [ 145 ] and 14 RCTs [ 129 , 144 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 , 154 , 155 , 156 , 157 ]. The studies included are described in Table 3 .…”

“…Four studies analysed the influence of antioxidant supplementation on DR onset or the degree of DR progression [ 145 , 146 , 151 , 153 ]. Three of them found a significant delay in DR progression in patients receiving Nutrof Omega ® or grape seed proanthocyanidins extract (GSPE) supplementation, with follow-up periods of at least 12 months [ 145 , 146 , 151 ]. The group of Haritoglou et al examined the onset of DME, basing the diagnosis on a funduscopic evaluation according to the ETDRS criteria, as an OCT device was not available at all the centres.…”

“…Gastrointestinal events were potentially associated with the treatment that was administered, and drugs were withdrawn in four patients of the supplemented group vs. one in the placebo group. Sanz-González et al reported mild gastrointestinal discomfort related to Nutrof Omega ® treatment, but no rates are specified and supplementation was not withdrawn [ 145 ].…”

“…Lafuente et al analysed the erythrocyte content of DHA and obtained significant differences among supplemented and placebo groups [ 129 , 149 ]. Sanz-González et al measured vitamin C levels and encountered inappropriate bioavailabilities, depending on different genetic expressions of SLC23A2 (which regulates intracellular levels of the vitamin), in the context of chronic hyperglycaemia and DR [ 145 ]. In addition, Haritoglou et al, who reported nonsignificant clinical results and did not measure supplemented α-lipoic acid levels, postulated that administered doses might have not been enough to produce retinal changes, because the ideal dose in humans has not yet been established in comparison to well-defined safety levels in animal assays [ 154 ].…”

Signature of Circulating Biomarkers in Recurrent Non-Infectious Anterior Uveitis. Immunomodulatory Effects of DHA-Triglyceride. A Pilot Study

“…Nutrition and nutritional control have been suggested as potential interventions for slowing the progression of several diseases, such as ocular surface dysfunction dry eyes (OSD), glaucoma, diabetic retinopathy (DR), or age-related macular degeneration (AMD), much of these with controversial results [ 16 , 17 , 18 , 19 , 20 , 21 ]. It has been shown that docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid (ω3 PUFA), and its anti-inflammatory derivatives (series-3 prostaglandins, resolvin D1, neuroprotectin D1, maresin, etc.)…”