Kato Masatomo, Kurose Tatsuji, Oda Tomoko, Miyaji Suguru
Research & Development Division, Santen Pharmaceutical Co, Ltd, Nara, Japan.
J Ocul Pharmacol Ther. 2003 Aug;19(4):315-24. doi: 10.1089/108076803322279372.
Platelet-activating factor (PAF) may be an important mediator in allergic conjunctivitis. In this study, apafant, a potent PAF antagonist, was evaluated for topical ocular anti-PAF activity in PAF and antigen stimulated conjunctivitis models. PAF, when injected into parpebral conjunctiva, provoked an acute increase, measured as dye leakage, in conjunctival vascular permeability. Apafant inhibited this response in a dose-related manner, and the inhibitory action of 0.1% apafant lasted for at least 6 hours duration. PAF, when instilled into the conjunctival sac, induced itch-scratching behavior and clinical symptoms, such as conjunctival redness and edema. These were inhibited by pretreatment with apafant ophthalmic solution. In a passive conjunctival anaphylaxis model in guinea pigs, significant inhibition of the allergic response was observed following topical ocular administration of apafant 5 and 15 minutes prior to the antigen challenge. We have demonstrated that PAF plays an important role in the development of allergic conjunctivitis. These results clearly indicate that apafant has potential as a topical ocular anti-PAF for treating allergic conjunctivitis.
血小板活化因子(PAF)可能是过敏性结膜炎的重要介质。在本研究中,对强效PAF拮抗剂阿帕泛在PAF和抗原刺激的结膜炎模型中的局部眼用抗PAF活性进行了评估。将PAF注射到睑结膜中时,会引起结膜血管通透性的急性增加,以染料渗漏来衡量。阿帕泛以剂量相关的方式抑制这种反应,0.1%阿帕泛的抑制作用持续至少6小时。将PAF滴入结膜囊时,会诱发搔抓行为和临床症状,如结膜充血和水肿。阿帕泛滴眼液预处理可抑制这些症状。在豚鼠被动结膜过敏模型中,在抗原攻击前5分钟和15分钟局部眼用阿帕泛后,观察到过敏反应受到显著抑制。我们已经证明PAF在过敏性结膜炎的发展中起重要作用。这些结果清楚地表明,阿帕泛作为一种局部眼用抗PAF药物治疗过敏性结膜炎具有潜力。