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J. J. Chae, T. Hongyok, Y. J. Shin, D. Na, Y. Nishi, R. S. Chuck; Sex - Related Response in the Botulinum Toxin B-Induced Mouse Model of Dry Eye. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3664.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate sex-related response in the botulinum toxin B (BTX-B) induced mouse model of dry eye.
Twenty each of male and female CBJ mice were randomly separated into 2 groups: Group 1 was injected with 20mU/0.05ml BTX-B and Group 2 was injected with 0.05ml normal saline into the left lacrimal gland, respectively. Tear production, corneal staining and blink rate were recorded at baseline, 3days, 1, 2, 4 weeks. All mice were euthanized and ocular surfaces and lacrimal glands harvested at 4 weeks after injection. Real time (RT) polymerase chain reaction(PCR) for β-actin, MIF, Tollip, IL-1b, IL-10, IL-12a and TNF- and immunohistochemistry for MIF and TNF- were performed for each sample.
Tear production was significantly decreased at from 3days (Male: 2.18±0.51 and 2.93±0.47, P=0.22; Female 2.38±0.66 and 3.09±0.42 P=0.13) to 4weeks (Male: 2.44±0.45 and 3.46±0.60 P<0.001; Female 2.41±0.35 and 3.40±0.51, P=0.001) after injection compared to control in both sexes. Corneal staining was significantly increased in both sexes compared to control. Increase in corneal staining was observed at 3days (2.78±1.20 and 0.82±0.82, P=0.22) and 4weeks (2.89±0.75 and 0.6±0.69, P<0.001) in females, and at 1 week (1.92±0.99 and 0.52±0.79, P=0.03) and 4weeks (3.2±0.92 and 0.67±1.01, P<0.001) in males after injection. However, there are no significant differences between BTX-B injected male and female in tear production and corneal staining. Also, we could not find any differences in blink rate between any of the groups. PCR study of lacrimal glands showed that BTX-B injected groups were induced to express significantly more MIF expression (Male: 0.94±0.09 and 0.80±0.02, P<0.001; Female 1.09±0.27 and 0.86±0.12 P=0.28) than control groups. The study of ocular surface showed that BTX-B injected groups were induced to express significantly more TNF- (Male: 1.06±0.12 and 0.66±0.02, P<0.001; Female 1.12±0.07 and 0.67±0.03 P=0.01) than control groups. However, there are no significant differences between BTX-B injected males and females. Immunohistochemistry studies confirmed increased expression MIF in the lacrimal gland in BTX-B injected both groups.
Intralacrimal BTX-B injection can successfully induce dry eye changes in both male and female mice. However, there were no significantly differences in between male and female mice in tear production, corneal staining and inflammatory cytokine responses.
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