Protective effect of TPP-Niacin on microgravity-induced oxidative stress and mitochondrial dysfunction of retinal...

Adverse effects of spaceflight on the human body are attritubuted to microgravity and space radiation. One of the most sensitive organs affected by them is the eye, particularly the retina. The conditions that astronauts suffer, such as visual acuity, is collectively called a spaceflight-associated neuro-ocular syndrome (SANS); however, the underlying molecular mechanism of the microgravity-induced ocular pathogenesis is not clearly understood. The current study explored how microgravity affects the retina function in ARPE19 cells in vitro under time-averaged simulated microgravity (μG) generated by clinostat. We found multicellular spheroid (MCS) formation and a significantly decreased cell migration potency under μG conditions compared to 1G in ARPE19 cells. We also observed that μG increases intracellular reactive oxygen species (ROS) and causes mitochondrial dysfunction in ARPE19 cells. Subsequently, we showed that μG activates autophagic pathways and ciliogenesis. Furthermore, we demonstrated that mitophagy activation is triggered via the mTOR-ULK1-BNIP3 signaling axis. Finally, we validated the effectiveness of TPP-Niacin in mitigating μG-induced oxidative stress and mitochondrial dysfunction in vitro, which provides the first experimental evidence for TPP-Niacin as a potential therapeutic agent to ameliorate the cellular phenotypes caused by μG in ARPE19 cells. Further investigations are, however, required to determine its physiological functions and biological efficacies in primary human retinal cells, in vivo models, and target identification.