title: Serine protease inhibitor A3K suppressed the formation of ocular surface squamous metaplasia in a mouse model of experimental dry eye.
abstract: OBJECTIVE
  To investigate the effects and possible mechanisms of serine protease inhibitor A3K (SERPINA3K) on the formation of ocular surface squamous metaplasia in a mouse dry eye model induced by topical benzalkonium chloride (BAC).
  
  
  METHODS
  The eye drops containing SERPINA3K were topically administered during the induction of BAC-induced dry eye. The clinical indications of dry eye were evaluated on day (D)16, including tear break-up time (BUT), tear volume, corneal fluorescein staining, and inflammatory index. Global specimens were collected on D16 and the following examinations were performed: histologic investigation, immunostaining of cytokeratin 10 (K10), p63 and Ki67 in the cornea, and Western blot analysis of tumor necrosis factor-α (TNF-α).
  
  
  RESULTS
  Serine protease inhibitor A3K suppressed the formation of BAC-induced dry eye, presenting with longer BUTs, lower corneal fluorescein staining scores, and inflammatory index, while no significant changes in tear volume. It also reduced the severity of abnormal differentiation and proliferation on ocular surface with lower expressions of K10, p63, and Ki67, and retained the number of goblet cells in the conjunctival fornix. Serine protease inhibitor A3K significantly decreased the levels of TNF-α in the cornea.
  
  
  CONCLUSIONS
  Topical application of SERPINA3K ameliorated the severity of ocular surface squamous metaplasia and suppressed the formation of BAC-induced dry eye.
authors.affiliation: Affiliated Xiamen Eye Center and Eye Institute of Xiamen University, Xiamen, China.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Affiliated Xiamen Eye Center and Eye Institute of Xiamen University, Xiamen, China Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, China.
authors.forename: Yueping
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Affiliated Xiamen Eye Center and Eye Institute of Xiamen University, Xiamen, China Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, China.
authors.forename: Yuqian
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Affiliated Xiamen Eye Center and Eye Institute of Xiamen University, Xiamen, China Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Affiliated Xiamen Eye Center and Eye Institute of Xiamen University, Xiamen, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Affiliated Xiamen Eye Center and Eye Institute of Xiamen University, Xiamen, China Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, China.
authors.forename: Pingping
authors.initials: P
authors.lastname: Luo
authors.affiliation: Affiliated Xiamen Eye Center and Eye Institute of Xiamen University, Xiamen, China Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, China.
authors.forename: Hui
authors.initials: H
authors.lastname: He
authors.affiliation: Affiliated Xiamen Eye Center and Eye Institute of Xiamen University, Xiamen, China.
authors.forename: Huping
authors.initials: H
authors.lastname: Wu
authors.affiliation: Affiliated Xiamen Eye Center and Eye Institute of Xiamen University, Xiamen, China Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, China.
authors.forename: Zuguo
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019573:Epithelium, Corneal / Q000187:drug effects*; D005451:Fluorescein Angiography; D008297:Male; D008679:Metaplasia / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D015843:Serpins / Q000494:pharmacology*; D013666:Tears / Q000378:metabolism
chemical_list: D015842:Serine Proteinase Inhibitors; D015843:Serpins; C051324:kallistatin
keywords: dry eye; inflammation; serine proteinase inhibitor; squamous metaplasia