miR-874 ameliorates retinopathy in diabetic rats by NF-κB signaling pathway

Background: The increased activation of the NF-κB signaling pathway contributes to the progression of retinopathy in diabetic rats.

Objectives: Using bioinformatics tools, we identified a potential binding site for miR-874 on the NF-κB p65 subunit. Based on this, we hypothesized that miR-874 could improve diabetic retinopathy by inhibiting the NF-κB signaling pathway.

Materials and Methods: Ten healthy rats were used as the control group. Sixty rats with streptozotocin (STZ)-induced diabetes (60 mg/kg) were randomly assigned to the following groups: model group (normal saline injection), negative control (NC) agomir group (NC mimic injection), miR-874 agomir group (miR-874 mimic injection), miR-874 anti-agomir group (miR-874 inhibitor injection), EVP4593 group (NF-κB pathway antagonist EVP4593 injection), and miR-874 anti-agomir + EVP4593 group (miR-874 inhibitor + EVP4593 injection). All injections were administered via the caudal vein.

Results: miR-874 was found to target the degradation of the p65 subunit. Compared to the control group, rats in the model group exhibited reduced miR-874 expression, increased levels of vascular endothelial growth factor (VEGF) and Ang2 proteins, as well as decreased end-diastolic velocity (EDV), peak systolic velocity (PSV) of the central retinal artery (CRA), and blood flow velocities in both the central retinal artery (CRA) and vein (CRV). Additionally, plasma viscosity (PV), blood viscosity (BV), erythrocyte sedimentation rate (ESR), capillary pericytes (IPCs), and vascular endothelial cells (VECs) were altered, and p65 expression in the retina was elevated (all p < 0.05). These findings indicate the presence of pathological changes in the retina of diabetic rats. In contrast, rats treated with the miR-874 mimic or EVP4593 showed improvements in these indices, while those treated with the miR-874 inhibitor exhibited further deterioration (all p < 0.05). EVP4593 also alleviated the worsening of retinopathy caused by miR-874 inhibition.

Conclusions: miR-874 improves diabetic retinopathy by modulating the NF-κB signaling pathway through targeting the degradation of p65. These results demonstrate the potential therapeutic benefit of miR-874 in diabetic retinopathy.