Effects of topical anti-inflammatory agents in a botulinum toxin B-induced mouse model of keratoconjunctivitis sicca

Kaevalin Lekhanont, Choul Yong Park, Janine A. Smith, Juan Castro Combs, Pisit Preechawat, Olan Suwan-Apichon, Ram Rangsin, Roy S. Chuck

Research output: Contribution to journalArticle

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Abstract

Purpose: The aim of this study was to compare the effects of topical nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroid, doxycycline, and artificial tears for the treatment of ocular surface damage in the Botulinum toxin B (BTX-B)-induced mouse model of dry eye. Methods: CBA/J mice were randomized into 2 experimental groups of 35 animals each. The control group received a transconjunctival injection of 0.05 mL of saline into the left lacrimal gland, and another group was injected with 0.05 mL of 20 milliunits BTX-B solution (SPSS, Inc., Chicago, IL). Three (3) days after intralacrimal gland injections, each group was equally randomized into 7 subgroups (n = 5 each) to receive treatment unilaterally into their left eyes with topical artificial tears (0.5% carboxymethylcellulose sodium), 0.1% fluorometholone, 0.1% nepafenac, 0.4% ketorolac, 0.09% bromfenac, 0.1% diclofenac, or 0.025% doxycycline. Tear volume, ocular surface changes, and spontaneous blink rate were evaluated in each of the 14 experimental subgroups. Results: Topical fluorometholone, nepafenac, and doxycycline significantly improved corneal surface staining in the BTX-B-injected mice within 2 weeks of treatment. Topical ketorolac, diclofenac, and bromfenac, applied twice-daily, partially reduce corneal staining, and did so more slowly by the 4-week time point. In comparison, topical artificial tear-treated mice did not demonstrate significant improvement of the corneal surface at any time point. Aqueous tear production in the BTX-B-injected fluorometholone-treated group started to return to baseline level within 2 weeks, although not significantly. Meanwhile, BTX-B-injected mice treated with artificial tears, topical NSAIDs, and doxycycline still exhibited a reduction in tear production up to 4 weeks. No significant differences in blink rate between the control and study groups undergoing the various treatments were noted at all time points. Conclusions: This study suggests the potential usefulness of topical NSAIDs, corticosteroid, and doxycycline for the clinical treatment of ocular surface epithelial disorders associated with dry eye.

Original languageEnglish (US)
Pages (from-to)27-34
Number of pages8
JournalJournal of Ocular Pharmacology and Therapeutics
Volume23
Issue number1
DOIs
StatePublished - Feb 2007
Externally publishedYes

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Keratoconjunctivitis Sicca
Doxycycline
Fluorometholone
Anti-Inflammatory Agents
Tears
Ketorolac
Diclofenac
Adrenal Cortex Hormones
Pharmaceutical Preparations
Staining and Labeling
Therapeutics
Lacrimal Apparatus
Inbred CBA Mouse
Control Groups
Carboxymethylcellulose Sodium
Injections
rimabotulinumtoxinB
Lubricant Eye Drops

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Ophthalmology
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Effects of topical anti-inflammatory agents in a botulinum toxin B-induced mouse model of keratoconjunctivitis sicca. / Lekhanont, Kaevalin; Park, Choul Yong; Smith, Janine A.; Combs, Juan Castro; Preechawat, Pisit; Suwan-Apichon, Olan; Rangsin, Ram; Chuck, Roy S.

In: Journal of Ocular Pharmacology and Therapeutics, Vol. 23, No. 1, 02.2007, p. 27-34.

Research output: Contribution to journalArticle

Lekhanont, Kaevalin ; Park, Choul Yong ; Smith, Janine A. ; Combs, Juan Castro ; Preechawat, Pisit ; Suwan-Apichon, Olan ; Rangsin, Ram ; Chuck, Roy S. / Effects of topical anti-inflammatory agents in a botulinum toxin B-induced mouse model of keratoconjunctivitis sicca. In: Journal of Ocular Pharmacology and Therapeutics. 2007 ; Vol. 23, No. 1. pp. 27-34.
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abstract = "Purpose: The aim of this study was to compare the effects of topical nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroid, doxycycline, and artificial tears for the treatment of ocular surface damage in the Botulinum toxin B (BTX-B)-induced mouse model of dry eye. Methods: CBA/J mice were randomized into 2 experimental groups of 35 animals each. The control group received a transconjunctival injection of 0.05 mL of saline into the left lacrimal gland, and another group was injected with 0.05 mL of 20 milliunits BTX-B solution (SPSS, Inc., Chicago, IL). Three (3) days after intralacrimal gland injections, each group was equally randomized into 7 subgroups (n = 5 each) to receive treatment unilaterally into their left eyes with topical artificial tears (0.5{\%} carboxymethylcellulose sodium), 0.1{\%} fluorometholone, 0.1{\%} nepafenac, 0.4{\%} ketorolac, 0.09{\%} bromfenac, 0.1{\%} diclofenac, or 0.025{\%} doxycycline. Tear volume, ocular surface changes, and spontaneous blink rate were evaluated in each of the 14 experimental subgroups. Results: Topical fluorometholone, nepafenac, and doxycycline significantly improved corneal surface staining in the BTX-B-injected mice within 2 weeks of treatment. Topical ketorolac, diclofenac, and bromfenac, applied twice-daily, partially reduce corneal staining, and did so more slowly by the 4-week time point. In comparison, topical artificial tear-treated mice did not demonstrate significant improvement of the corneal surface at any time point. Aqueous tear production in the BTX-B-injected fluorometholone-treated group started to return to baseline level within 2 weeks, although not significantly. Meanwhile, BTX-B-injected mice treated with artificial tears, topical NSAIDs, and doxycycline still exhibited a reduction in tear production up to 4 weeks. No significant differences in blink rate between the control and study groups undergoing the various treatments were noted at all time points. Conclusions: This study suggests the potential usefulness of topical NSAIDs, corticosteroid, and doxycycline for the clinical treatment of ocular surface epithelial disorders associated with dry eye.",
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AU - Combs, Juan Castro

AU - Preechawat, Pisit

AU - Suwan-Apichon, Olan

AU - Rangsin, Ram

AU - Chuck, Roy S.

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N2 - Purpose: The aim of this study was to compare the effects of topical nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroid, doxycycline, and artificial tears for the treatment of ocular surface damage in the Botulinum toxin B (BTX-B)-induced mouse model of dry eye. Methods: CBA/J mice were randomized into 2 experimental groups of 35 animals each. The control group received a transconjunctival injection of 0.05 mL of saline into the left lacrimal gland, and another group was injected with 0.05 mL of 20 milliunits BTX-B solution (SPSS, Inc., Chicago, IL). Three (3) days after intralacrimal gland injections, each group was equally randomized into 7 subgroups (n = 5 each) to receive treatment unilaterally into their left eyes with topical artificial tears (0.5% carboxymethylcellulose sodium), 0.1% fluorometholone, 0.1% nepafenac, 0.4% ketorolac, 0.09% bromfenac, 0.1% diclofenac, or 0.025% doxycycline. Tear volume, ocular surface changes, and spontaneous blink rate were evaluated in each of the 14 experimental subgroups. Results: Topical fluorometholone, nepafenac, and doxycycline significantly improved corneal surface staining in the BTX-B-injected mice within 2 weeks of treatment. Topical ketorolac, diclofenac, and bromfenac, applied twice-daily, partially reduce corneal staining, and did so more slowly by the 4-week time point. In comparison, topical artificial tear-treated mice did not demonstrate significant improvement of the corneal surface at any time point. Aqueous tear production in the BTX-B-injected fluorometholone-treated group started to return to baseline level within 2 weeks, although not significantly. Meanwhile, BTX-B-injected mice treated with artificial tears, topical NSAIDs, and doxycycline still exhibited a reduction in tear production up to 4 weeks. No significant differences in blink rate between the control and study groups undergoing the various treatments were noted at all time points. Conclusions: This study suggests the potential usefulness of topical NSAIDs, corticosteroid, and doxycycline for the clinical treatment of ocular surface epithelial disorders associated with dry eye.

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