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T. Hongyok, Y. J. Shin, M. Cano, R. S. Chuck; Strain-Related Response in the Botulinum Toxin-Induced Mouse Model of Dry Eye. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5333.
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© ARVO (1962-2015); The Authors (2016-present)
To test strain-related response in the botulinum toxin B (BTX-B) induced mouse model of dry eye in both BALB/c and C57/BL6 backgrounds.
Ten each of BALB/c and C57/BL6 mice were randomly assigned to 2 groups: Group I - 20 mU BTX-B in 0.05 mL; Group II - 0.05 mL normal saline control right intralacrimal gland injections. Corneal staining, tear production and blink rate were recorded at baseline, 3 days, 1, 2, 4 and 6 weeks when all mice were euthanized and ocular surfaces and lacrimal glands harvested. Real-time (RT) PCR for β-actin, MIF, Tollip, IL-1b, IL-10, IL-12a and TNF-α and immunofluorescence studies of TNF-α, IL-1b and MIF were performed
At baseline, both groups displayed mild corneal staining. BTX-B injection induced dry eye in both strains with significant increase in corneal fluorescein staining observed at 2-4 weeks post-injection compared to control (wk2; 3.6±0.59 and 2.0±1.0, p<.001 and wk4; 3.1±0.87 and 2.4±0.96, p=0.04). Tear production was not significantly reduced by BTX-B in either strain (at wk2; C57/BL6 2.28±1.55 and 2.04±0.43, p=0.66, BALB/c 3.14±1.83 and 4.10±1.46, p=0.22). Blink rate was comparable between groups at all time points in both strains (wk2; 1.55±2.01 and 1.18±1.54, p=0.53). BALB/c demonstrated significantly greater tear production and blink rate than C57/BL6 in both groups. PCR study of the lacrimal glands showed that BTX-B injection significantly induced more MIF expression in C57/BL6 (90.8±70.4 and 7.7±6.0, p=0.018) but not in BALB/c (5.9±1.6 and 16.0±17.5, p=0.37). Ocular surface PCR studies of C57/BL6 showed that IL-12a was significantly increased (0.087±0.01 and 0.011±0.005, p=0.03) while Tollip was significantly decreased by BTX injection (0.000006±0.000002 and 0.0007±0.0, p=0.002). In BALB/c, surface inflammatory cytokines were not significantly changed. Immunofluorescence studies confirmed greater MIF expression in the lacrimal glands and ocular surfaces was induced by BTX-B injection in C57/BL6 compared to BALB/c.
Intralacrimal BTX-B gland injection can successfully induce dry eye in both BALB/c and C57/BL6 mouse backgrounds. However, each strain displays different blink rates, tear production and strain related inflammatory cytokines responses.
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