Extracellular vesicles promote epithelial-to-mesenchymal transition of lens epithelial cells under oxidative stress

Abstract

Posterior capsule opacification (PCO), resulting from residual lens epithelial cell (LEC) epithelial-mesenchymal transition (EMT), abnormal proliferation, and migration, is the most common complication of cataract surgery. A recent study determined that extracellular vesicles (EVs) and reactive oxygen species (ROS) regulate the EMT process during cutaneous wound healing and tumour metastasis. However, their underlying mechanism in PCO is unclear. In this study, we examined the secreted EVs from a scratch model in vitro. We found that the production of ROS was increased after mechanical injury, especially at the wound edge, and there was an increased viability of LECs, which can be blocked by diphenyleneiodonium, an NADPH oxidase inhibitor. Cell viability and migration were increased upon treatment with 1 μM H₂O₂, but significantly reduced when the concentration of H₂O₂ increased to 100 μM. Transwell assay showed that both post-surgery LECs and LECs treated with 1 μM H₂O₂ significantly induced the migration of normal LECs by EV secretion. Extraction and quantification of EVs derived from injured and H₂O₂-treated LECs showed a similar increase in production. Co-incubation of EVs from both injured and H₂O₂-treated LECs with normal LECs and organ-cultured mouse lenses activated EMT, which was attenuated by a ROS inhibitor. These results suggest that EVs participate in ROS-induced lens EMT, making EVs a potential target for treating PCO.

Keywords: Epithelial-mesenchymal transition; Extracellular vesicles; Lens epithelial cells; Posterior capsule opacification; Reactive oxygen species.