Corneal alternations induced by topical application of benzalkonium chloride in rabbit

• Published in: PloS one 2011-10, Vol.6 (10), p.e26103
• Main Authors: Chen, Wensheng, Li, Zhiyuan, Hu, Jiaoyue, Zhang, Zhenhao, Chen, Lelei, Chen, Yongxiong, Liu, Zuguo
• Format: Article
• Language: English
• Subjects: Actomyosin; Actomyosin - metabolism; Administration, Topical; Alternations; Animals; Antimicrobial agents; B cells; Benzalkonium chloride; Benzalkonium Compounds - administration & dosage; Benzalkonium Compounds - toxicity; Biology; Chloride; Chlorides; Comparative analysis; Confocal microscopy; Conjunctiva; Conjunctiva - drug effects; Cornea; Cornea - drug effects; Cornea - pathology; Corneal Stroma - drug effects; Corneal Stroma - pathology; Dislocation; Dislocations; Disruption; Edema; Endothelial cells; Endothelium; Endothelium, Corneal - drug effects; Epithelium, Corneal - drug effects; Epithelium, Corneal - pathology; Evaluation; Eye; Eye (anatomy); Fluorescein; Fluoresceins - metabolism; Fluorescent Antibody Technique; Immunofluorescence; Laboratory animals; Male; Medicine; Membrane Proteins - metabolism; Microscopy; Microscopy, Confocal; Microscopy, Fluorescence; Mucin; Mucins; Ophthalmic agents; Permeability; Permeability - drug effects; Phosphoproteins - metabolism; Preservatives; Protein expression; Proteins; Rabbits; Staining; Staining and Labeling; Studies; Surface active agents; Tearing; Tears - drug effects; Topical application; Tumor necrosis factor-TNF; Zonula Occludens-1 Protein
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0026103

Benzalkonium chloride (BAC) is the most common preservative in ophthalmic preparations. Here, we investigated the corneal alternations in rabbits following exposure to BAC. Twenty-four adult male New Zealand albino rabbits were randomly divided into three groups. BAC at 0.01%, 0.05%, or 0.1% was applied twice daily to one eye each of rabbits for 4 days. The contralateral untreated eyes were used as control. Aqueous tear production and fluorescein staining scores of BAC-treated eyes were compared with those of controls. The structure of the central cornea was examined by in vivo confocal microscopy. Expression of mucin-5 subtype AC (MUC5AC) in conjunctiva was detected by immunostainig on cryosections. Corneal barrier function was assessed in terms of permeability to carboxy fluorescein (CF). The distribution and expression of ZO-1, a known marker of tight junction, and reorganization of the perijunctional actomyosin ring (PAMR) were examined by immunofluorescence analysis. Although there were no significant differences between control and BAC-treated eyes in Schirmer scores, corneal fluorescein scores and the number of conjunctival MUC5AC staining cells, in vivo confocal microscopy revealed significant epithelial and stromal defects in all BAC-treated corneas. Moreover, BAC at 0.1% resulted in significant increases in central corneal thickness and endothelial CF permeability, compared with those in control eyes, and endothelial cell damage with dislocation of ZO-1 and disruption of PAMR. Topical application of BAC can quickly impair the whole cornea without occurrence of dry eye. A high concentration of BAC breaks down the barrier integrity of corneal endothelium, concomitant with the disruption of PAMR and remodeling of apical junctional complex in vivo.