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.

氧化应激诱导的视网膜色素上皮细胞（RPE）功能障碍是导致早期干龄相关性黄斑变性（AMD）的主要因素。视网膜的氧化损伤可能促进RPE释放的细胞外囊泡（EV）。在这项研究中，我们研究了氧化诱导的RPE细胞来源的微粒（RMP）对RPE细胞功能的影响。所述氧化应激诱导的从RPE细胞释放更多的RMP在体外和体内，并且从年轻的RPE细胞释放的RMP明显比从年轻的RPE细胞释放的RMP多得多。RMP细胞以时间依赖性方式吸收RMP。然而，CD36的阻滞减弱了吸收过程。此外，通过RMPs处理降低RPE细胞活力与细胞周期蛋白依赖性激酶抑制剂p15和p21表达增加有关。RMP增强RPE细胞的衰老并中断吞噬活性。本研究表明，RMPs具有强烈的诱导RPE细胞变性的作用。这一发现进一步支持了RMPs加剧RPE细胞氧化应激损伤的假设，这可能揭示了干性AMD发生的潜在相关过程。