title: Localization and expression of zonula occludins-1 in the rabbit corneal epithelium following exposure to benzalkonium chloride.
abstract: Preservatives are a major component of the ophthalmic preparations in multi-dose bottles. The purpose of this study was to investigate the acute effect of benzalkonium chloride (BAC), a common preservative used in ophthalmic preparations, on the localization and expression of zonula occludens (ZO)-1 in the rabbit corneal epithelium in vivo. BAC at 0.005%, 0.01%, or 0.02% was topically applied to one eye each of albino rabbits at 5 min intervals for a total of 3 times. The contralateral untreated eyes served as controls. The following clinical indications were evaluated: Schirmer test, tear break-up time (BUT), fluorescein and rose Bengal staining. The structure of central cornea was examined by in vivo confocal microscopy, and the corneal barrier function was evaluated by measurement of corneal transepithelial electrical resistance and permeability to carboxy fluorescein. Whole mount corneas were analyzed by using fluorescence confocal microscopy for the presence of ZO-1, 2, occludin, claudin-1, Ki67 and cell apoptosis in the epithelium. The expression of ZO-1 in the corneal epithelium was also examined by western blot and reverse transcription-polymerase chain reaction analyses. Exposure to BAC resulted in higher rose Bengal staining scores while no significant changes in BUT, Schirmer and corneal florescein scores. It also induced corneal epithelial cell damage, dispersion of ZO-1 and ZO-2 from their normal locus at the superficial layer and disruption of epithelial barrier function. However, the amounts of ZO-1 mRNA and protein in the corneal epithelium were not affected by BAC treatment. Exposure to BAC can quickly impair the corneal epithelium without tear deficiency. BAC disrupts the tight junctions of corneal epithelium between superficial cells in the rabbit corneal epithelium in vivo.
authors: Eye Institute and affiliated Xiamen Eye Center of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Vision Science, Fujian, China. cwensheng@hotmail.com
authors: Wensheng
authors: W
authors: Chen
authors: Jiaoyue
authors: J
authors: Hu
authors: Zhenhao
authors: Z
authors: Zhang
authors: Lelei
authors: L
authors: Chen
authors: Hui
authors: H
authors: Xie
authors: Nuo
authors: N
authors: Dong
authors: Yongxiong
authors: Y
authors: Chen
authors: Zuguo
authors: Z
authors: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001548:Benzalkonium Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D062445:Claudin-1 / Q000378:metabolism; D017097:Electric Impedance; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019573:Epithelium, Corneal / Q000187:drug effects* / Q000378:metabolism*; D005452:Fluoresceins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D018613:Microscopy, Confocal; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D062826:Zonula Occludens-1 Protein / Q000235:genetics / Q000378:metabolism*; D062827:Zonula Occludens-2 Protein / Q000378:metabolism
chemical_list: D001548:Benzalkonium Compounds; D062445:Claudin-1; D005452:Fluoresceins; D019394:Ki-67 Antigen; D012333:RNA, Messenger; D062826:Zonula Occludens-1 Protein; D062827:Zonula Occludens-2 Protein; C024098:6-carboxyfluorescein