Abstract
BackgroundDry eye is a common disease worldwide, and animal models are critical for the study of it. At present, there is no research about the stability of the extant animal models, which may have negative implications for previous dry eye studies. In this study, we observed the stability of a rabbit dry eye model induced by the topical benzalkonium chloride (BAC) and determined the valid time of this model.Methods and FindingsEighty white rabbits were randomly divided into four groups. One eye from each rabbit was randomly chosen to receive topical 0.1% BAC twice daily for 2 weeks (Group BAC-W2), 3 weeks (Group BAC-W3), 4 weeks (Group BAC-W4), or 5 weeks (Group BAC-W5). Fluorescein staining, Schirmer's tests, and conjunctival impression cytology were performed before BAC treatment (normal) and on days 0, 7, 14 and 21 after BAC removal. The eyeballs were collected at these time points for immunofluorescence staining, hematoxylin and eosin (HE) staining, and electron microscopy. After removing BAC, the signs of dry eye in Group BAC-W2 lasted one week. Compared with normal, there were still significant differences in the results of Schirmer's tests and fluorescein staining in Groups BAC-W3 and BAC-W4 on day 7 (P<0.05) and in Group BAC-W5 on day 14 (P<0.05). Decreases in goblet cell density remained stable in the three experimental groups at all time points (P<0.001). Decreased levels of mucin-5 subtype AC (MUC5AC), along with histopathological and ultrastructural disorders of the cornea and conjunctiva could be observed in Group BAC-W4 and particularly in Group BAC-W5 until day 21.ConclusionsA stable rabbit dry eye model was induced by topical 0.1% BAC for 5 weeks, and after BAC removal, the signs of dry eye were sustained for 2 weeks (for the mixed type of dry eye) or for at least 3 weeks (for mucin-deficient dry eye).
Highlights
Dry eye is a common disease worldwide [1]
A stable rabbit dry eye model was induced by topical 0.1% benzalkonium chloride (BAC) for 5 weeks, and after BAC removal, the signs of dry eye were sustained for 2 weeks or for at least 3 weeks
Group BAC-W2 was medicated for 2 weeks, Group BAC-W3 was medicated for 3 weeks, Group BAC-W4 was medicated for 4 weeks, and Group BAC-W5 was medicated for 5 weeks
Summary
Dry eye is a common disease worldwide [1]. Clinical epidemiological surveys have demonstrated that in 1995, 17% of the outpatients in Japan reported symptoms of dry eye [2], and in 1997, 14.6% of the U.S population who ranged in age from 65 to 84 years showed symptoms of dry eye [3]. In 2003, approximately 33.7% of the elderly population of Taiwan (those over the age of 65 years) reported symptoms of dry eye [4]. Dry eye is a common disease worldwide, and animal models are critical for the study of it. There is no research about the stability of the extant animal models, which may have negative implications for previous dry eye studies. We observed the stability of a rabbit dry eye model induced by the topical benzalkonium chloride (BAC) and determined the valid time of this model
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