Simulated microgravity promotes oxidative stress-induced apoptosis in ARPE-19 cells associated with Nrf2 signaling pathway

Spaceflight associated neuro-ocular syndrome (SANS) has become a high-risk complication for astronauts in the microgravity environment. Growing evidences suggest that altered hemodynamics of the cerebrospinal fluid system under microgravity may affect optic nerve-related structures and lead to ocular diseases. Retinal pigment epithelial (RPE) cells play a pivotal role in maintaining the blood-retinal barrier, participating in the metabolism of visual circulation. Previous study has observed that the structure, shape, adhesion, migration and angiogenesis of RPE cells were significantly changed under microgravity. However, the interrelated molecular mechanisms underlying the cytological functions of RPE cells under microgravity have yet to be elucidated. Here, we exposed ARPE-19 cells in Random Positioning Machine (RPM) system. The preliminary analysis of cytological functions found that the viability of ARPE-19 cells was decreased and the cell cycle was arrested in S phase. Further results revealed that elevated ROS in microgravity caused oxidative stress, resulting in the activation of the Nrf2-HO-1 pathway. Meanwhile, cells subjected to oxidative damage result in apoptosis by regulating the expression of apoptosis-related genes. Taken together, these findings have significant implications for the understanding the molecular mechanism of SANS.