Extracellular microparticles exacerbate oxidative damage to retinal pigment epithelial cells

Abstract

Oxidative stress-induced retinal pigment epithelial cell (RPE) dysfunction is a primary contributing factor to early dry age-related macular degeneration (AMD). Oxidative injury to the retina may promote extracellular vesicles (EVs) released from RPE. In this study, we investigated the effects of oxidative-induced RPE cell-derived microparticles (RMPs) on RPE cell functions. The oxidative stress induced more RMPs released from RPE cells in vitro and in vivo, and significant more RMPs were released from aged RPE cells than that from younger RPE cells. RMPs were taken up by RPE cells in a time-dependent manner; however, blockage of CD36 attenuated the uptake process. Furthermore, the decrease of RPE cell viability by RMPs treatment was associated with an increased expression of cyclin-dependent kinase inhibitors p15 and p21. RMPs enhanced senescence and interrupted phagocytic activity of RPE cells as well. The present study demonstrated that RMPs produce a strong effect of inducing RPE cell degeneration. This finding further supports the postulate that RMPs exacerbate oxidative stress damage to RPE cells, which may uncover a potentially relevant process in the genesis of dry AMD.

Keywords: Extracellular vesicles; Oxidative stress; Phagocytosis; RPE cell Dysfunction; RPE cell-Derived microparticles (RMPs); Retinal pigment epithelial cell (RPE); Senescence.