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Effects of Exposure to Ozone on the Ocular Surface in an Experimental Model of Allergic Conjunctiviti

 Hun Lee  ;  Eung Kweon Kim  ;  Hee Young Kim  ;  Tae-im Kim 
 PLoS One, Vol.12(1) : e0169209, 2017 
Journal Title
 PLoS One 
Issue Date
Animals ; Antioxidants/metabolism ; Butylated Hydroxyanisole/pharmacology ; Cell Survival/drug effects ; Cells, Cultured ; Conjunctiva/drug effects ; Conjunctiva/pathology ; Conjunctivitis, Allergic/pathology* ; Cytokines/metabolism ; Disease Models, Animal ; Environmental Exposure/analysis* ; Epithelial Cells/drug effects ; Epithelial Cells/metabolism ; Eye/drug effects ; Eye/pathology* ; Female ; Fluorescein/metabolism ; Inflammation Mediators/metabolism ; Interleukin-1alpha/pharmacology ; Interleukin-6/pharmacology ; Mice, Inbred BALB C ; Mitochondria/drug effects ; Mitochondria/metabolism ; Mitochondrial Proteins/metabolism ; Oxidative Stress/drug effects ; Ozone/adverse effects* ; Staining and Labeling ; Tears/metabolism ; Treatment Outcome ; Tumor Necrosis Factor-alpha/metabolism
Based on previous findings that ozone can induce an inflammatory response in the ocular surface of an animal model and in cultured human conjunctival epithelial cells, we investigated whether exposure to ozone exacerbates symptoms of allergic conjunctivitis. We evaluated the effects of exposure to ozone on conjunctival chemosis, conjunctival injection, corneal and conjunctival fluorescein staining scores, production of inflammatory cytokines in tears, and aqueous tear production in a mouse model of allergic conjunctivitis. To validate our in vivo results, we used interleukin (IL)-1α-pretreated conjunctival epithelial cells as an in vitro substitute for the mouse model. We evaluated whether exposure to ozone increased the inflammatory response and altered oxidative status and mitochondrial function in IL-1α-pretreated conjunctival epithelial cells. In the in vivo study, ozone induced increases in conjunctival chemosis, conjunctival injection, corneal and conjunctival fluorescein staining scores, and production of inflammatory cytokines, accompanied by a decrease in tear volume. In the in vitro study, exposure to ozone led to additional increases in IL-6 and tumor necrosis factor-α mRNA levels, which were already induced by treatment with IL-1α. Ozone did not induce any changes in cell viability. Pretreatment with IL-1α increased the expression of manganese superoxide dismutase, and exposure to ozone led to additional increments in the expression of this antioxidant enzyme. Ozone did not induce any changes in mitochondrial activity or expression of mitochondrial enzymes and proteins related to mitochondrial function, with the exception of phosphor-mammalian target of rapamycin. Treatment with butylated hydroxyanisole, a free radical scavenger, attenuated the ozone-induced increases in IL-6 expression in IL-1α-pretreated conjunctival epithelial cells. Therefore, we conclude that exposure to ozone exacerbates the detrimental effects on the integrity of the ocular surface caused by conjunctival allergic reactions, and further increases the inflammatory response in IL-1α-pretreated conjunctival epithelial cells.
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1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
Yonsei Authors
김응권(Kim, Eung Kweon) ORCID logo https://orcid.org/0000-0002-1453-8042
김태임(Kim, Tae Im) ORCID logo https://orcid.org/0000-0001-6414-3842
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