Changes in the ocular surface induced by
ozone have received limited research attention. Here, we investigate the effects of
ozone exposure on the integrity of the ocular surface, the production of inflammatory
cytokines in tears, and changes in
mucin-secreting cells in a mouse model. In addition,
ozone-induced nuclear factor-κB (NF-κB)-mediated inflammatory processes were evaluated in cultured human conjunctival epithelial cells. In vivo,
ozone induced the breakdown of corneal epithelial integrity, decreased the number of
mucin-secreting cells, and induced the production of inflammatory
cytokines, without altering tear volume. In vitro,
ozone exposure led to increases in NF-κB nuclear translocation, κB-dependent transcriptional activity, NF-κB inhibitor α (IκBα) proteolysis, and expression of phosphorylated IκBα (p-IκBα), but did not cause cytotoxicity or cellular apoptosis. In addition,
ozone induced the expression of inflammatory
cytokines,
Toll-like receptors, and
C-C chemokine receptors, but decreased the expression of
mucins. Furthermore, inhibition of NF-κB with
pyrrolidine dithiocarbamate before exposure of cultured human conjunctival epithelial cells to
ozone prevented changes in IκBα and p-IκBα levels in association with a decrease in the levels of inflammatory
cytokines. Therefore, we conclude that
ozone exposure interferes with ocular surface integrity and induces
inflammation involving NF-κB-mediated processes at the level (and/or upstream) of IκBα. Understanding the role of
ozone in the initiation of inflammatory processes on the animal ocular surface and in cultured human conjunctival epithelial cells can help elucidate the pathogenesis of ocular surface damage and suggest protective strategies for preserving a healthy ocular surface against
ozone exposure.