title: A mouse dry eye model induced by topical administration of benzalkonium chloride.
abstract: OBJECTIVE
  To develop a dry eye model of mouse induced by topical administration of benzalkonium chloride (BAC) and investigate the possible mechanisms.
  
  
  METHODS
  BAC at concentration of 0.2% was applied to the mouse ocular surface for 7 days. Phenol red thread tear test, tear break-up time (BUT) test, corneal inflammatory index scoring, fluorescein and rose bengal test were performed to evaluate the toxic effects of BAC on the ocular surface. Global specimens were collected on day (D) 7 and labeled with a series of antibodies including cytokeratin 10 (K10) and mucin 5AC (MUC5AC). Apoptosis of ocular surface epithelium was evaluated by in situ terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Histologic analysis and transmission electron microscopy (TEM) were performed on D7.
  
  
  RESULTS
  BAC at a concentration of 0.2% successfully induced a dry eye condition with decreased tear volume and BUTs, increased corneal fluorescein and rose bengal scores. The Inflammatory index was increased in accompaniment with higher tumor necrosis factor-α (TNF-α) expression and more inflammatory infiltration in the cornea. Immunolabeling revealed positive K10 expression in BAC-treated corneal epithelium and fewer MUC5AC-positive cells in the BAC-treated conjunctival fornix. TUNEL assay showed more apoptotic cells in the corneal basal epithelium. TEM showed that the size and intervals of the microvillis were both reduced in the corneal epithelium.
  
  
  CONCLUSIONS
  Topical administration of 0.2% BAC in mouse induces changes resembling that of dry eye syndrome in humans, and thus, represents a novel model of dry eye.
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, People’s Republic of China.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Lin
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Liu
authors.forename: Tong
authors.initials: T
authors.lastname: Zhou
authors.forename: Yihui
authors.initials: Y
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Bai
authors.forename: Hui
authors.initials: H
authors.lastname: He
authors.forename: Zuguo
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000287:Administration, Topical; D000818:Animals; D001548:Benzalkonium Compounds / Q000008:administration & dosage*; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000188:drug therapy*; D019793:Fluorescein / Q000494:pharmacology; D020287:In Situ Nick-End Labeling; D007249:Inflammation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008871:Microvilli / Q000378:metabolism; D010637:Phenolsulfonphthalein / Q000494:pharmacology; D011310:Preservatives, Pharmaceutical / Q000008:administration & dosage; D012395:Rose Bengal / Q000494:pharmacology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001548:Benzalkonium Compounds; D011310:Preservatives, Pharmaceutical; D014409:Tumor Necrosis Factor-alpha; D012395:Rose Bengal; D010637:Phenolsulfonphthalein; D019793:Fluorescein