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S. Miyaji, K. Imoto, M. Kato, K. Nakata; Apafant, a Potent Platelet Activating Factor Antagonist, Can Block Eosinophil Activation and is Effective in the Chronic Phase of Experimental Allergic Conjunctivitis . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3749.
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Purpose: To elucidate a role of platelet activating factor (PAF) in the pathophysiology of allergic conjunctivitis and to confirm the efficacy of apafant ophthalmic solution in the experimental allergic conjunctivitis. Methods: Guinea pigs were actively immunized on day zero by subconjunctival injection of ovalbumin absorbed on alminum hydroxide gel. Chronic allergic conjunctivitis was induced by repetitive instillation of antigen solution on days 14 and 16. Exp. 1) On day 17, 0.1% PAF solution was topically applied to confirm if PAF can activate eosinophils in the conjunctival tissues. Eosinophil activation was assessed by measuring the eosinophil peroxidase (EPO) activity in the tear. To assess the effect of apafant on the eosinophil activation, apafant ophthalmic solution was administered 15 and 5 minutes prior to the PAF instillation. Exp. 2) To assess the effect of apafant on the experimental allergic conjunctivitis, apafant ophthalmic solution was topically administered q.i.d through day 13 to day 16, and allergic conjunctivitis was repetitively induced on days 14 and 16. Itch-scratching episodes of animals were counted for 30 minutes after the antigen challenge and clinical symptoms were evaluated 30 minutes after the antigen challenge on a scale of 0 to 4. Results: Exp. 1) By instillation of PAF solution into the eyes of guinea pigs which were in the state of chronic allergic conjunctivitis, significant increase of EPO activity in tear fluid was observed, and the increase of EPO activity was inhibited by pre-treatment of apafant ophthalmic solution. Exp. 2) Compared to controls, animals treated with apafant ophthalmic solution had significant reduction of clinical symptoms and itch-scratching response both on day 14 and on day 16. The inhibitory effects of apafant ophthalmic solution were more prominent on day 16. Conclusions: PAF has an activity to induce mediator release from eosinophils in conjunctival tissues and may be deeply involved in the chronic phase of allergic conjunctivitis. Apafant ophthalmic solution inhibits eosinophil activation and is effective on chronic allergic conjunctivitis.
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