Dry eye induced by exposure to cigarette smoke pollution: An in vivo and in vitro study

Exposure to cigarette smoke (CS) pollution has previously associated with dry eye symptoms but without detailed experimental data and elucidation of the mechanism. We aimed to evaluate the effects of CS on the ocular surfaces of mice and the extraction of DMSO lipid-soluble cigarette smoke particles (DCSP) on cultured human corneal epithelial cells (HCECs), and explore to elucidate the probable mechanism. C57BL mice were exposed to CS challenging. In vivo clinical evaluations, including corneal fluorescein staining, tear film break-up time, and confocal microscopic observations, were performed before exposure and post-exposure. At the end of the in vivo study, changes in corneal and conjunctival histology, corneal ultrastructure, and conjunctival goblet cell intensity were examined, expression of TUNLE and Ki67 in tissue were also detected. In vitro, cell confluence and caspase3/7 were assessed in DCSP treated HCECs. Production of TNF-α, IL-1β and IL-6, activation of NF-κB and Ki67 were evaluated by means of ELISA and Western blot respectively in HCECs cultured with 0.6 μL/mL DCSP. We found that longer-term CS exposure induced dry eye symptoms in mice. Additionally, corneal and conjunctival epithelial damage occurred, the corneal ultrastructure changed, and the density of goblet cells decreased. Apoptosis and Ki67 increased in both the conjunctiva and the cornea of CS-exposed animals. Furthermore, although DCSP inhibited the proliferation of HCECs, expression of Ki67 increased and apoptosis was only induced significantly by 2.0 μL/mL DCSP. The release of IL-1β and IL-6, activation of NF-κB were prompted by DCSP. The results indicated that CS is toxic to the ocular surface of mice and HCECs. Longer-term CS exposure in mice stimulates ocular surface changes that resemble those observed with dry eye. The mechanism may relate to inflammation and activation of NF-κB. In this study, we established a novel animal model to study dry eye, with the experimental data and elucidation of mechanism facilitating further research.