Shii Daisuke, Oda Tomoko, Shinomiya Katsuhiko, Katsuta Osamu, Nakamura Masatsugu
Research and Development Center, Santen Pharmaceutical Co. Ltd., Ikoma-shi, Nara, Japan.
J Ocul Pharmacol Ther. 2009 Aug;25(4):321-8. doi: 10.1089/jop.2009.0009.
The effects of cyclosporine A eye drops on the early-phase reaction were investigated in a type-I allergic conjunctivitis model.
Mice were actively sensitized with ragweed (RW) absorbed on aluminium hydroxide gel and challenged with RW for 10 days (single challenge model) or 10-14 days (repetitive challenge model) after the first sensitization. For the evaluation of itching, ovalbumin was used as an antigen instead of RW. The effects of cyclosporine A eye drops on increased vascular permeability, mast cell degranulation, and itching were evaluated and compared with those of other anti-allergic eye drops.
In the single challenge model, cyclosporine A eye drops significantly inhibited the increase in vascular permeability and histological evaluations showed suppressed degranulation of mast cells. Disodium cromoglycate (DSCG) eye drops showed only a slight tendency to inhibit the increase in both pathophysiological parameters. Ketotifen or betamethasone eye drops significantly inhibited the increase in vascular permeability. The order of potency in the single challenge model was ketotifen > cyclosporine A > betamethasone. In the repetitive challenge model, cyclosporine A eye drops significantly inhibited the increase in vascular permeability and DSCG eye drops showed only slight inhibition. Ketotifen or betamethasone significantly inhibited the increase in vascular permeability. The order of potency in the repetitive challenge model was cyclosporine A > betamethasone > ketotifen. The effect of cyclosporine A eye drops on the itch-scratch response was studied. Cyclosporine A and DSCG significantly reduced the itch-scratch response in the single and repetitive challenge models; the effect of cyclosporine A in the repetitive challenge model was more potent than in the single challenge model.
Those results suggest that administration of cyclosporine A eye drops inhibit the early-phase reaction in type-I allergic conjunctivitis, which may be mediated by the suppression of mast cell degranulation. This action of cyclosporine A eye drops may be involved in the therapeutic effect of cyclosporine A on allergic conjunctivitis.
在Ⅰ型过敏性结膜炎模型中研究环孢素A滴眼液对早期反应的影响。
用吸附于氢氧化铝凝胶上的豚草(RW)对小鼠进行主动致敏,并在首次致敏后10天(单次激发模型)或10 - 14天(重复激发模型)用RW进行激发。为评估瘙痒,用卵清蛋白代替RW作为抗原。评估环孢素A滴眼液对血管通透性增加、肥大细胞脱颗粒和瘙痒的影响,并与其他抗过敏滴眼液进行比较。
在单次激发模型中,环孢素A滴眼液显著抑制血管通透性增加,组织学评估显示肥大细胞脱颗粒受到抑制。色甘酸钠(DSCG)滴眼液仅显示出轻微抑制这两个病理生理参数增加的趋势。酮替芬或倍他米松滴眼液显著抑制血管通透性增加。单次激发模型中的效力顺序为酮替芬>环孢素A>倍他米松。在重复激发模型中,环孢素A滴眼液显著抑制血管通透性增加,DSCG滴眼液仅显示出轻微抑制作用。酮替芬或倍他米松显著抑制血管通透性增加。重复激发模型中的效力顺序为环孢素A>倍他米松>酮替芬。研究了环孢素A滴眼液对瘙痒 - 搔抓反应的影响。环孢素A和DSCG在单次和重复激发模型中均显著降低瘙痒 - 搔抓反应;环孢素A在重复激发模型中的作用比在单次激发模型中更强。
这些结果表明,给予环孢素A滴眼液可抑制Ⅰ型过敏性结膜炎的早期反应,这可能是通过抑制肥大细胞脱颗粒介导的。环孢素A滴眼液的这一作用可能参与了环孢素A对过敏性结膜炎的治疗效果。