A rabbit dry eye model induced by topical medication of a preservative benzalkonium chloride.
OBJECTIVE
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.
Xiong
Cuiju
C
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, People's Republic of China.
Chen
Dong
D
Liu
Jingbo
J
Liu
Bingqian
B
Li
Naiyang
N
Zhou
Yang
Y
Liang
Xuanwei
X
Ma
Ping
P
Ye
Chengtian
C
Ge
Jian
J
Wang
Zhichong
Z
D000287:Administration, Topical; D000818:Animals; D001548:Benzalkonium Compounds / Q000633:toxicity*; D002452:Cell Count; D003228:Conjunctiva / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D003315:Cornea / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015590:Fluorophotometry; D020397:Goblet Cells / Q000187:drug effects / Q000473:pathology; D008855:Microscopy, Electron, Scanning; D055271:Mucin 5AC; D009077:Mucins / Q000378:metabolism; D011310:Preservatives, Pharmaceutical / Q000633:toxicity*; D011817:Rabbits; D012395:Rose Bengal; D013666:Tears / Q000378:metabolism
D001548:Benzalkonium Compounds; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D009077:Mucins; D011310:Preservatives, Pharmaceutical; D012395:Rose Bengal