Thioredoxin1 is a target to attenuate diabetes‑induced RPE cell dysfunction in human ARPE19 cells by alleviating oxidative stress

Abstract

Diabetes-induced cell dysfunction of the retinal pigment epithelium (RPE) contributes to the initiation and progression of diabetic retinopathy (DR). Thioredoxin 1 (Trx1) plays a key role in DR. However, the effect and mechanism of Trx1 on diabetes-induced cell dysfunction of the RPE is not fully understood during DR. In the present study, the effect of Trx1 on this process and its related mechanism were investigated. A Trx1 overexpression cell line, ARPE19-Trx1/LacZ, was constructed and treated with or without high glucose (HG). Flow cytometry was used to analyze apoptosis of these cells and the mitochondrial membrane potential was analyzed using JC-1 staining solution. A DCFH-DA probe was also used to detect the reactive oxygen species (ROS) generation. Western blotting was used to examine the expression of related proteins in ARPE-19 cells after HG treatment. The results demonstrated that the RPE layer was damaged in clinical samples. ROS formation and RPE cell dysfunction increased after HG treatment in vitro . Besides, the expression of mitochondrial-mediated apoptosis related proteins (Bax, apoptosis-inducing factor, cytochrome C, Caspase3 and Caspase9) also increased; however, overexpression of Trx1 attenuated these changes and improved the function of ARPE19 cells. These results indicated that overexpression of Trx1 alleviated diabetes-induced RPE cell dysfunction in DR by attenuating oxidative stress.