Cigarette smoke induces ROS mediated autophagy impairment in human corneal epithelial cells.

Abstract

Cigarette smoke is an important indoor air pollutant which has deleterious effects on human health. Continued daily exposure to cigarette smoke has been attributed to the risk factor of ocular surface diseases. However, the mechanisms underlying the ocular surface damage are not fully elucidated. In this study, exposure to cigarette smoke extract (CSE) induced a dose- and time-dependent cytotoxicity in human corneal epithelial (HCE) cells, supported by the observation of reduced cell viability, increased apoptotic cells, elevated intracellular oxidative stress and loss of mitochondrial transmembrane potential. In addition, CSE exposure led to the impairment of proteostasis and autophagy, which resulted in the accumulation of ubiquitinated proteins as aggregates in peri-nuclear spaces. Furthermore, the autophagy inducer, cysteamine was shown to attenuate the CSE induced cell damage, oxidative stress and mitochondrial dysfunction in HCE cells. Moreover, cysteamine inhibited the formation of ubiquitin-positive aggregates around the peri-nuclear region, through regulating the autophagic activity of HCE cells. Similar to in\xa0vitro experiments, cigarette smoke induced proteostasis and autophagy impairment in corneal epithelial cells could be rescued by cysteamine in a cigarette smoke-exposed murine model. Therefore, this study may provide first evidence that dysfunction of autophagy contributes to the pathogenesis of ocular surface diseases associated with cigarette smoke exposure. Besides, it also suggests the potential therapeutic value of cysteamine in the prevention and treatment of cigarette smoke induced ocular surface injury. CSE induces cytotoxicity and accumulation of ubiquitinated proteins in HCE cells due to impairment of proteostasis and autophagy, which can be rescued by cysteamine.