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Jong Suk Song, Xiangzhe Li, Boram Kang, Youngsub Eom, Hyo Myung Kim; Effects of topical mucolytic agents on the Tear and Ocular Surface: a mucin-deficient dry eye model. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3296.
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A topical mucolytic agent, N-acetylcysteine (NAC), has been used to induce an animal model with loss of intestinal mucin layer. In this study, we investigated the effects of topical NAC on the tear and ocular surface in rats. In addition, the therapeutic effects of a mucin secretogogue, 3% diquafosol tetrasodium on the mucin-deficient ocular surface were evaluated.
The NAC-treated or control models were established by topically administering 10% NAC or normal saline 4 times a day for 5 days in male Sprague–Dawley rats. Clinical parameters, including tear volume, corneal wetting ability, corneal fluorescein staining scores, and ocular surface rose bengal staining scores were measured. The expressions of mucin proteins and genes were analyzed by enzyme-linked immunosorbent assay or real-time polymerase chain reaction in the tear and ocular tissue after NAC treatment. The alterations of conjunctival epithelium and goblet cells were observed by PAS staining, H&E staining, and scanning electron microscopy (SEM). Furthermore, the NAC-treated rats were divided into saline group and diquafosol group and treated with normal saline or 3% diquafosol solutions for 5 days. Clinical parameters and tear MUC5AC level were compared between the two groups.
The NAC-treated group showed significant decreases in tear secretion, corneal wetting ability, tear MUC5AC concentration, and conjunctival goblet cell numbers compared with the control group (all P<0.01). In addition, significant increases in corneal fluorescein score and rose bengal scores were observed in the NAC-treated group compared with the control group (P<0.05, P<0.01, respectively). H&E staining and SEM clearly showed damages in conjunctival epithelial cell layer in the NAC group. Although there was no significant difference in MUC16 gene expression, the MUC16 concentrations of tear and ocular tissue were significantly increased in the NAC- treated group than the control group (P<0.01, P<0.05, respectively). Five day treatment with 3% diquafosol tetrasodium showed only minimal therapeutic effects in the NAC-treated rat eyes.
Topical administration of 10% NAC induced ocular surface damages and tear film instability by affecting MUC16 to be disrupted and released from ocular surface. This animal model would be used to study dry eye disease, especially for the mucin-deficiency subtype.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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