Jauhonen Hanna-Mari, Laihia Jarmo, Oksala Olli, Viiri Johanna, Sironen Reijo, Alajuuma Päivi, Kaarniranta Kai, Leino Lasse
Department of Ophthalmology, Kuopio University Hospital, Kuopio, Finland.
Institute of Clinical Medicine, Department of Ophthalmology, University of Eastern Finland, Kuopio, Finland.
Graefes Arch Clin Exp Ophthalmol. 2017 Dec;255(12):2357-2362. doi: 10.1007/s00417-017-3781-z. Epub 2017 Aug 24.
Our purpose was to investigate the effect of locally administered cis-urocanic (cis-UCA) in two experimental models of allergic conjunctivitis.
The compound 48/80 (C48/80)-induced ocular irritation model (IgE-independent) and the ovalbumin (OA)-induced ocular allergy model (IgE-mediated) were used to test and compare the effect of cis-UCA on dexamethasone, ketotifen and olopatadine. In the C48/80 model, clinical severity scoring from photographs, immunohistochemical analysis of nuclear Ki-67 antigen to quantify actively proliferating epithelial cells and of caspase-3 enzyme to identify apoptotic activity in the conjunctival tissue were used. In the OA model, an Evans Blue stain concentration of conjunctival tissue was used to evaluate vascular leakage due to allergic reaction.
The cis-UCA was well tolerated and effective in both the IgE-independent and -mediated rat models. Treatment with C48/80 caused conjunctival hyperaemia, which was significantly inhibited by ketotifen at the 6 h time point (p = 0.014) and by dexamethasone and cis-UCA 0.5% at 12 (p = 0.004) and 24 (p = 0.004) hour time points. In a comparison between the active drug treatments, only ketotifen showed a significant difference (p = 0.023) to cis-UCA treatment at the 1 h time point, otherwise there were no statistically significant differences between the active drugs. Ketotifen, dexamethasone and cis-UCA 0.5% significantly inhibited the C48/80-induced nuclear accumulation of Ki-67, without differences between the active treatment groups. In the OA model, cis-UCA 0.5% did not inhibit the vascular leakage of conjunctiva, whereas cis-UCA 2.5% of was at least equally effective compared to olopatadine, abolishing the allergic vascular leakage response almost completely.
The present findings in the two AC models suggest that cis-UCA might have anti-allergic potency both in immediate and delayed-type allergic reactions in the eye.
我们的目的是在两种过敏性结膜炎实验模型中研究局部应用顺式尿刊酸（cis-UCA）的效果。
使用化合物48/80（C48/80）诱导的眼部刺激模型（非IgE依赖性）和卵清蛋白（OA）诱导的眼部过敏模型（IgE介导）来测试和比较cis-UCA与地塞米松、酮替芬和奥洛他定的效果。在C48/80模型中，通过对照片进行临床严重程度评分、对核Ki-67抗原进行免疫组织化学分析以量化结膜组织中活跃增殖的上皮细胞、对caspase-3酶进行免疫组织化学分析以识别结膜组织中的凋亡活性。在OA模型中，使用结膜组织的伊文思蓝染色浓度来评估过敏反应引起的血管渗漏。
cis-UCA在非IgE依赖性和IgE介导的大鼠模型中耐受性良好且有效。用C48/80处理导致结膜充血，在6小时时间点酮替芬（p = 0.014）、在12小时（p = 0.004）和24小时（p = 0.004）时间点地塞米松和0.5%的cis-UCA可显著抑制。在活性药物治疗之间的比较中，仅在1小时时间点酮替芬与cis-UCA治疗有显著差异（p = 0.023），否则活性药物之间无统计学显著差异。酮替芬、地塞米松和0.5%的cis-UCA显著抑制C48/80诱导的Ki-67核积累，活性治疗组之间无差异。在OA模型中，0.5%的cis-UCA不抑制结膜血管渗漏，而2.5%的cis-UCA与奥洛他定相比至少同样有效，几乎完全消除过敏血管渗漏反应。
在两种过敏性结膜炎模型中的当前发现表明，cis-UCA在眼部的速发型和迟发型过敏反应中可能都具有抗过敏效力。
