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(Investigative Ophthalmology and Visual Science. 2008;49:1850-1856.)
© 2008 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.07-0720
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A Rabbit Dry Eye Model Induced by Topical Medication of a Preservative Benzalkonium Chloride

Cuiju Xiong,1 Dong Chen,2 Jingbo Liu,1 Bingqian Liu,1 Naiyang Li,1 Yang Zhou,1 Xuanwei Liang,1 Ping Ma,1 Chengtian Ye,1 Jian Ge,1 and Zhichong Wang1

1From the State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, People’s Republic of China; and the 2First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China.

PURPOSE. To establish a rabbit dry eye model with topical medication of the ocular preparation preservative benzalkonium chloride (BAC).

METHODS. Sixteen white rabbits were used. One eye of each rabbit was chosen randomly for topical administration of 0.1% BAC twice daily for 14 days. The other untreated eyes served as controls. Schirmer test, fluorescein, and rose bengal staining were performed before and after BAC treatment on days 3, 5, 7, and 14. Conjunctiva impression cytology specimens were collected on days 0, 7, and 14. The rabbits were killed after day 14. Immunofluorescence staining was performed to detect mucin-5 subtype AC (MUC5AC) on conjunctival cryosections. Cornea and conjunctiva structures were evaluated by light and electron microscopy.

RESULTS. Compared with untreated controls, BAC-treated eyes showed significant decreases in Schirmer scores (P = 0.01) and increases in fluorescein scores (P < 0.001) on days 5, 7, and 14. A significant increase in rose bengal scores was noticed as early as day 3 (P = 0.001). Decreases in goblet cell density occurred on days 7 and 14 (P = 0.001). Decreased MUC5AC and histopathologic and ultrastructural disorders of the cornea and conjunctiva were also observed in the BAC group.

CONCLUSIONS. These findings demonstrated that an ophthalmic preservative, benzalkonium chloride, induced a dry eye syndrome in rabbits with damage to the cornea and conjunctiva, decreased aqueous tear basal secretion, goblet cell loss, and MUC5AC deficiency. This rabbit model was consistent with human dry eye syndrome in both aqueous tear and mucin deficiency and may be appropriate for studying dry eye syndrome.






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