Interaction of miR-146a-5p with oxidative stress and inflammation in complications of type 2 diabetes mellitus in male rats: antioxidant and anti-inflammatory protection strategies in type 2 diabetic retinopathy

Objective(s): This study aimed to evaluate the role of miR-146a-5p in the pathogenesis of diabetic retinopathy and its interaction with oxidative stress and inflammation in the ocular tissue of rats with type 2 diabetes mellitus (T2DM). Materials and Methods: Twenty adult male Sprague Dawley rats (220 +/- 20 g) were randomly assigned to control and diabetic groups. A high-fat diet was used for three months to induce T2DM which was confirmed by the HOMA-IR index. After that, the levels of glucose and insulin in serum, HOMA-IR as an indicator of insulin resistance, the ocular level of oxidative markers, TNF-alpha, IL-1 beta, MIPs, and MCP-1 along with ocular gene expression of NF-kappa B, Nrf2, and miR-146a-5p were evaluated. Results: The level of lipid peroxidation along with metabolic and inflammatory factors significantly increased and the antioxidant enzyme activity significantly decreased in diabetic rats (P<0.05). The ocular expression of NF-kappa B and TNF-alpha increased and Nrf2, HO-1, and miR-146a-5p expression decreased in diabetic rats (P<0.05). In addition, a negative correlation between miR-146a-5p expression with NF-kappa B and HOMA-IR and a positive correlation between miR-146a-5p with Nrf2 were observed. Conclusion: It can be concluded that miR-146a-5p may regulate Nrf2 and NF-kappa B expression and inflammation and oxidative stress in the ocular tissue of diabetic rats.