Long Noncoding RNA MEG3 Inhibits Apoptosis of Retinal Pigment Epithelium Cells Induced by High Glucose via the miR-93/Nrf2 Axis.

Diabetic retinopathy (DR) is the leading cause of visual impairment in developed nations. Though plasma miR-93 is associated with the risk of DR, the function and regulatory mechanism of miR-93 during DR remains unclear. Blood samples were collected from 12 DR patients and 12 healthy controls. Primary human RPE cells and ARPE-19 cells were cultured in 5 mmol/L or 33 mmol/L d-glucose medium. LncRNA maternally expressed gene 3 (MEG3) and miR-93 expression was detected by real-time quantitative PCR. The effect of MEG3 and miR-93 on high glucose (HG)-induced apoptosis was detected by MTT and flow cytometry. IL-6 and tumor necrosis factor-α (TNF-α) levels were detected by enzyme-linked immunosorbent assay. The relationships among MEG3, miR-93, and nuclear factor erythroid 2-related factor 2 (Nrf2) were explored via dual-luciferase reporter assay. LncRNA MEG3 and Nrf2 were decreased and miR-93 was increased in blood samples of DR patients, and HG-treated human RPE and ARPE-19 cells. Overexpression of miR-93 inhibited cell proliferation and promoted apoptosis, whereas overexpression of Nrf2 or MEG3 promoted proliferation and suppressed apoptosis and inflammation. In addition, MEG3 targeted miR-93 and down-regulated miR-93. Moreover, miR-93 directly targeted Nrf2 and negatively regulated Nrf2. This study suggests that lncRNA MEG3 depresses HG-induced apoptosis and inflammation of retinal pigment epithelium via miR-93/Nrf2 axis, providing a novel perspective on the genesis and development of DR.