Curcumin inhibits high glucose‑induced inflammatory injury in human retinal pigment epithelial cells through the ROS‑PI3K/AKT/mTOR signaling pathway.

Abstract

Diabetic retinopathy (DR) is a retinal disease caused by metabolic disorders of glucose tolerance that can lead to irreversible blindness if not adequately treated. Retinal pigment epithelial cell (RPEC) dysfunction contributes to the pathogenesis of DR. In the present study the anti-inflammatory effect of curcumin (CUR) was investigated in RPECs damaged by high glucose levels. RPEC treated with 30 mmol/l glucose was regarded as high glucose group, and cells treated with 24.4 mmol/l mannitol was set as equivalent osmolarity group. Cell Counting Kit-8 assay was used to measure RPEC viability, the expression of phosphorylated (p)-AKT and p-mammalian target of rapamycin (mTOR) were assessed by western blot, and secretion of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β in the culture medium was measured by ELISA. Intracellular reactive oxygen species (ROS) levels were measured by laser scanning confocal microscope. The present data indicated that, compared with mannitol treatment, high glucose treatment reduced RPEC viability, increased TNF-α, IL-6 and IL-1β secretion, increased ROS formation and promoted phosphorylation of AKT and mTOR. The antioxidant N-acetylcysteine, the phosphoinositide 3-kinase (PI3K)/AKT inhibitor LY294002 and the mTOR inhibitor rapamycin ameliorated the effects of high glucose. In addition, pretreatment with 10 µmol/l CUR reduced secretion levels of TNF-α, IL-6 and IL-1β, ROS formation and phosphorylation of AKT and mTOR. In conclusion, CUR inhibited high glucose-induced inflammatory injury in RPECs by interfering with the ROS/PI3K/AKT/mTOR signaling pathway. The present study may reveal the molecular mechanism of CUR inhibition effects to high glucose-induced inflammatory injury in RPEC.