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M. Rizen, O. Suwan–apichon, J.M. G. Reyes, S. Herretes, R.S. Chuck; Botulinum Toxin B Induced Mouse Model of Keratoconjunctivitis Sicca . Invest. Ophthalmol. Vis. Sci. 2005;46(13):4469.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To develop a chronic mouse model of keratoconjunctivitis sicca. Methods: Under direct visualization using an operating microscope, CBA/J mice received transconjunctival injections of either saline or 1.25, 5 or 20 milliunits of botulinum toxin B (BTX–B) into the lacrimal gland. The mice were either left unstressed or subjected to a blower for 5 hours/day, 5 days/week. Tear production and corneal fluorescein staining were evaluated for all groups before injection and at several time points following injection. Tear production was measured with phenol red impregnated cotton threads. Corneal fluorescein staining was photographed under cobalt blue light using a digital camera fitted with a macro lens. Results: After 4 days, saline injected mice showed no corneal staining, while BTX–B injected mice showed various amounts of corneal staining, with an apparent dose response. At this early time point, there did not appear to be an additional effect from the blower on corneal fluorescein staining. After 1 week, BTX–B injected mice had significantly decreased aqueous tear production. The mean tear production for the saline group was 3.13 + 0.2 mm compared to 1.88 + 0.1 mm, 1.88 + 0.1 mm and 1.50 + 0.1 for the 1.25, 5 and 20 mU BTX–B groups, respectively (p = 0.02, p = 0.02, p = 0.01). Mice subjected to a dessicating stress had similar aqueous tear production. The mean tear production for the saline + blower group was 3.00 + 0.2 mm (p = 0.41). The mean tear production for the BTX–B + blower groups was 0.88 + 0.2 mm, 1.50 + 0.3 mm and 1.50 + 0.1 mm for the 1.25, 5 and 20 mU groups, respectively (p = 0.003, p = 0.03, p = 0.005). Conclusions: Intra–lacrimal gland injection of botulinum toxin B results in corneal fluorescein staining within 4 days and a significant decrease in aqueous tear production which persists for at least 1 week. Therefore, this may represent a viable mouse model of keratoconjunctivitis sicca. Ongoing studies will evaluate the chronicity of the condition, effect on corneal permeability, and conjunctival and lacrimal gland histopathology.
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