Delay of Diabetic Cataract Progression by a Chemical Chaperone Trimethylamine N-Oxide through Alleviating Unfolded-Protein-Induced ER Stress

This study aims to investigate the protective effects of trimethylamine N-oxide (TMAO), a natural occurring chaperone, on delaying diabetic cataract (DC) progression. In vivo and ex vivo, TMAO reduced high glucose (HG)-induced lens opacity and EMT in rat lens epithelial cells (LECs).

In vitro experiments demonstrated that HG resulted in enhanced apoptosis, migration, ROS and EMT-related genes in HLE-B3 cells while TMAO addition diminished these effects. RNA-seq revealed that the inhibition of ER stress was the key factor to reverse the impacts of HG on LECs by TMAO and mechanistic investigations suggested that ER stress-related pathway were significantly inhibited in TMAO treated LECs under HG or tunicamycin-induced ER stress.