Botulinum toxin B-induced mouse model of keratoconjunctivitis sicca

Olan Suwan-Apichon, Michael Rizen, Ram Rangsin, Samantha Herretes, Johann M G Reyes, Kaevalin Lekhanont, Roy S. Chuck

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

PURPOSE. To develop a mouse model of human chronic dry eye (keratoconjunctivitis sicca [KCS]). METHODS. Under direct visualization with an operating microscope, CBA/J mice received a transconjunctival injection of saline or 1.25, 5, or 20 milliunits (mU) of botulinum toxin B (BTX-B) into the lacrimal gland. The mice were either left unstressed or were subjected to an air blower for 5 h/d, 5 d/wk in fixed temperature and humidity conditions. Tear production and corneal fluorescein staining were evaluated in all groups before injection and at several time points after. Tear production was measured with phenol red-impregnated cotton threads. Corneal fluorescein staining was photographed under cobalt blue light with a digital camera fitted with a macro lens. RESULTS. BTX-B-injected mice displayed significantly decreased tear production until the 4-week time point. Throughout all time points, the addition of environmental blower stress did not appear to alter tear production significantly. Linear regression models, used to evaluate the effects of various doses of BTX-B on tear production, showed that doses higher than 1.25 mU did not provide significantly different outcomes. After 3 days, saline-injected mice showed no corneal staining, whereas BTX-B-injected mice displayed various amounts of staining. At the early time point (day 3), there did not appear to be an additional effect of the blower on corneal fluorescein staining. However, at 1, 2, and 4 weeks, the blower stress appeared to increase the amount of corneal fluorescein staining at each BTX-B dose, although not significantly. Furthermore, at 8 to 10 weeks, in the BTX B-injected groups, corneas had persistent staining, even though tear production had already returned to normal levels. Histopathologic analyses revealed no inflammatory cell infiltration of the stroma or acini of the lacrimal glands and conjunctivae of both saline-injected and BTX-B-injected animals. CONCLUSIONS. Intralacrimal gland injection of BTX-B resulted in persistent corneal fluorescein staining within 3 days, and a significant decrease in aqueous tear production that persisted for 1 month. Intralacrimal gland injection of BTX-B suppressed lacrimation, thereby establishing a dry eye state. This animal model could be a useful tool for investigating the pathogenesis of the chronic condition KCS in humans.

Original languageEnglish (US)
Pages (from-to)133-139
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume47
Issue number1
DOIs
StatePublished - Jan 2006
Externally publishedYes

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Keratoconjunctivitis Sicca
Tears
Staining and Labeling
Fluorescein
Lacrimal Apparatus
Injections
Linear Models
Phenolsulfonphthalein
Inbred CBA Mouse
rimabotulinumtoxinB
Conjunctiva
Humidity
Cobalt
Cornea
Lenses
Animal Models
Air
Light
Temperature

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Suwan-Apichon, O., Rizen, M., Rangsin, R., Herretes, S., Reyes, J. M. G., Lekhanont, K., & Chuck, R. S. (2006). Botulinum toxin B-induced mouse model of keratoconjunctivitis sicca. Investigative Ophthalmology and Visual Science, 47(1), 133-139. https://doi.org/10.1167/iovs.05-0380

Botulinum toxin B-induced mouse model of keratoconjunctivitis sicca. / Suwan-Apichon, Olan; Rizen, Michael; Rangsin, Ram; Herretes, Samantha; Reyes, Johann M G; Lekhanont, Kaevalin; Chuck, Roy S.

In: Investigative Ophthalmology and Visual Science, Vol. 47, No. 1, 01.2006, p. 133-139.

Research output: Contribution to journalArticle

Suwan-Apichon, O, Rizen, M, Rangsin, R, Herretes, S, Reyes, JMG, Lekhanont, K & Chuck, RS 2006, 'Botulinum toxin B-induced mouse model of keratoconjunctivitis sicca', Investigative Ophthalmology and Visual Science, vol. 47, no. 1, pp. 133-139. https://doi.org/10.1167/iovs.05-0380
Suwan-Apichon O, Rizen M, Rangsin R, Herretes S, Reyes JMG, Lekhanont K et al. Botulinum toxin B-induced mouse model of keratoconjunctivitis sicca. Investigative Ophthalmology and Visual Science. 2006 Jan;47(1):133-139. https://doi.org/10.1167/iovs.05-0380
Suwan-Apichon, Olan ; Rizen, Michael ; Rangsin, Ram ; Herretes, Samantha ; Reyes, Johann M G ; Lekhanont, Kaevalin ; Chuck, Roy S. / Botulinum toxin B-induced mouse model of keratoconjunctivitis sicca. In: Investigative Ophthalmology and Visual Science. 2006 ; Vol. 47, No. 1. pp. 133-139.
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AU - Rangsin, Ram

AU - Herretes, Samantha

AU - Reyes, Johann M G

AU - Lekhanont, Kaevalin

AU - Chuck, Roy S.

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N2 - PURPOSE. To develop a mouse model of human chronic dry eye (keratoconjunctivitis sicca [KCS]). METHODS. Under direct visualization with an operating microscope, CBA/J mice received a transconjunctival injection of saline or 1.25, 5, or 20 milliunits (mU) of botulinum toxin B (BTX-B) into the lacrimal gland. The mice were either left unstressed or were subjected to an air blower for 5 h/d, 5 d/wk in fixed temperature and humidity conditions. Tear production and corneal fluorescein staining were evaluated in all groups before injection and at several time points after. Tear production was measured with phenol red-impregnated cotton threads. Corneal fluorescein staining was photographed under cobalt blue light with a digital camera fitted with a macro lens. RESULTS. BTX-B-injected mice displayed significantly decreased tear production until the 4-week time point. Throughout all time points, the addition of environmental blower stress did not appear to alter tear production significantly. Linear regression models, used to evaluate the effects of various doses of BTX-B on tear production, showed that doses higher than 1.25 mU did not provide significantly different outcomes. After 3 days, saline-injected mice showed no corneal staining, whereas BTX-B-injected mice displayed various amounts of staining. At the early time point (day 3), there did not appear to be an additional effect of the blower on corneal fluorescein staining. However, at 1, 2, and 4 weeks, the blower stress appeared to increase the amount of corneal fluorescein staining at each BTX-B dose, although not significantly. Furthermore, at 8 to 10 weeks, in the BTX B-injected groups, corneas had persistent staining, even though tear production had already returned to normal levels. Histopathologic analyses revealed no inflammatory cell infiltration of the stroma or acini of the lacrimal glands and conjunctivae of both saline-injected and BTX-B-injected animals. CONCLUSIONS. Intralacrimal gland injection of BTX-B resulted in persistent corneal fluorescein staining within 3 days, and a significant decrease in aqueous tear production that persisted for 1 month. Intralacrimal gland injection of BTX-B suppressed lacrimation, thereby establishing a dry eye state. This animal model could be a useful tool for investigating the pathogenesis of the chronic condition KCS in humans.

AB - PURPOSE. To develop a mouse model of human chronic dry eye (keratoconjunctivitis sicca [KCS]). METHODS. Under direct visualization with an operating microscope, CBA/J mice received a transconjunctival injection of saline or 1.25, 5, or 20 milliunits (mU) of botulinum toxin B (BTX-B) into the lacrimal gland. The mice were either left unstressed or were subjected to an air blower for 5 h/d, 5 d/wk in fixed temperature and humidity conditions. Tear production and corneal fluorescein staining were evaluated in all groups before injection and at several time points after. Tear production was measured with phenol red-impregnated cotton threads. Corneal fluorescein staining was photographed under cobalt blue light with a digital camera fitted with a macro lens. RESULTS. BTX-B-injected mice displayed significantly decreased tear production until the 4-week time point. Throughout all time points, the addition of environmental blower stress did not appear to alter tear production significantly. Linear regression models, used to evaluate the effects of various doses of BTX-B on tear production, showed that doses higher than 1.25 mU did not provide significantly different outcomes. After 3 days, saline-injected mice showed no corneal staining, whereas BTX-B-injected mice displayed various amounts of staining. At the early time point (day 3), there did not appear to be an additional effect of the blower on corneal fluorescein staining. However, at 1, 2, and 4 weeks, the blower stress appeared to increase the amount of corneal fluorescein staining at each BTX-B dose, although not significantly. Furthermore, at 8 to 10 weeks, in the BTX B-injected groups, corneas had persistent staining, even though tear production had already returned to normal levels. Histopathologic analyses revealed no inflammatory cell infiltration of the stroma or acini of the lacrimal glands and conjunctivae of both saline-injected and BTX-B-injected animals. CONCLUSIONS. Intralacrimal gland injection of BTX-B resulted in persistent corneal fluorescein staining within 3 days, and a significant decrease in aqueous tear production that persisted for 1 month. Intralacrimal gland injection of BTX-B suppressed lacrimation, thereby establishing a dry eye state. This animal model could be a useful tool for investigating the pathogenesis of the chronic condition KCS in humans.

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