May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Involvement of Cycloxygenase-1 and -2 in Ocular Inflammation and Pain Using a Rabbit Model
Author Affiliations & Notes
  • T. Ogawa
    Research and Development, Senju USA, Inc., Encino, California
  • T. Kida
    Research and Development, Senju USA, Inc., Encino, California
  • C. K. Song
    Medical Affairs, ISTA Pharmaceuticals, Inc., Irvine, California
  • J. A. Gow
    Medical Affairs, ISTA Pharmaceuticals, Inc., Irvine, California
  • T. R. McNamara
    Medical Affairs, ISTA Pharmaceuticals, Inc., Irvine, California
  • Footnotes
    Commercial Relationships T. Ogawa, None; T. Kida, None; C.K. Song, None; J.A. Gow, None; T.R. McNamara, None.
  • Footnotes
    Support None.
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 5834. doi:
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    • Get Citation

      T. Ogawa, T. Kida, C. K. Song, J. A. Gow, T. R. McNamara; Involvement of Cycloxygenase-1 and -2 in Ocular Inflammation and Pain Using a Rabbit Model. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5834.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose:: Bromfenac sodium (BF) is a potent inhibitor of both cyclooxygenase-1 and -2 (COX-1 and COX-2) and nimesulide (NS) is a selective COX-2 inhibitor. To evaluate BF and NS in the inhibition of COX-1 and COX-2 using various ocular inflammation and ocular pain severities in a rabbit model.

Methods:: Dutch belted rabbits were used and test drugs were prepared 0.1% ophthalmic solution. Inflammation model: a) Paracentesis: One hundred fifty µl of aqueous humor was aspirated with a 30 gauge syringe at 1 hr after instillation of one drop of test agent. The aqueous flare was measured with a flare cell meter (Kowa) for 3 hrs. b) Laser irradiation: The iris was irradiated at 6 spots equally spaced by argon laser at 1 hr after instillation of test agent and the aqueous flare was measured for 3 hrs. Pain model: a) Corneal sensitivity: The sensitivity of central cornea was evaluated using a Cochet-Bonnet esthesiometer for 3 hrs after instillation of test agent using oxybuprocaine 0.4% as the comparison. b) Chemical stimuli: Sodium hydroxide was applied to the cornea after instillation of test agent using oxybuprocaine 0.4% as the comparison and the distance between upper and lower palpebral fissure (mm) was measured by a caliper for 5 hrs.

Results:: BF inhibited the increase in aqueous protein production induced by paracentesis by 95%, whereas, NS exhibited no inhibitory activity. Laser irradiation gradually increased aqueous protein production with a peak at 1 hr. BF and NS demonstrated significant inhibitory activities in aqueous protein production by 88% and 58%, respectively. Oxybuprocaine 0.4% removed corneal sensitivity completely and BF reduced the corneal sensitivity threshold by 50% compared to oxybuprocaine. NS had no effect on the normal corneal sensitivity. Oxybuprocaine 0.4% did not show significant effect against sodium hydroxide-induced pain. In contrast, BF significantly reduced the ocular pain by 50% during 5 hrs.

Conclusions:: This study suggests that COX-1 responds acutely to direct mechanical stimulation of the eye. COX-2 is involved in moderate to severe inflammation and chemical burn-induced ocular pain. COX-2 demonstrates chronic responsiveness. Therefore, NSAIDs with equivalent inhibition in both COX-1 and COX-2 could potentially treat various mild to severe ocular inflammation and ocular pain conditions.

Keywords: inflammation • aqueous • ocular irritants 
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