From the *Department of Ophthalmology, Yamaguchi University Graduate School of Medicine, Ube City, Yamaguchi, Japan; and †Department of Ophthalmology, Kochi Medical School, Nankoku City, Kochi, Japan.
Cornea. 2010 Nov;29 Suppl 1:S62-7. doi: 10.1097/ICO.0b013e3181ea9b2b.
Severe ocular allergic diseases such as vernal keratoconjunctivitis are characterized not only by conjunctival allergic inflammation, including infiltration of T helper 2 cells and eosinophils into the conjunctiva, but also by various corneal disorders such as persistent epithelial defects and shield ulcer. Although the cornea and conjunctiva are thought to influence each other during ocular allergic inflammation, direct evidence for interaction between these tissues in vivo has been lacking. Eosinophils and eosinophil-derived factors are implicated in the pathogenesis of corneal lesions associated with ocular allergy, with cytotoxic granule proteins such as major basic protein and matrix metalloproteinase 9 derived from eosinophils having been detected in shield ulcer. Major basic protein exhibits cytotoxic effects in cultured corneal epithelial cells and inhibits corneal epithelial wound healing in organ culture, whereas matrix metalloproteinase 9 can degrade the corneal epithelial basement membrane. In vitro studies have revealed that cytokines and other inflammatory mediators directly impair the barrier function of corneal epithelial cells and increase the expression of chemokines and adhesion molecules by corneal stromal fibroblasts, effects that may enhance allergic inflammation. We have recently shown that removal of the corneal epithelium augmented late-phase clinical signs and conjunctival eosinophilia, whereas conjunctival inflammation delayed corneal epithelial wound healing, in a rat model of ocular allergy. Conjunctival allergic inflammation and corneal epithelial disorders thus interact with each other in vivo to generate a vicious cycle, interruption of which might provide the basis for novel approaches to the treatment of severe ocular allergy.
严重的眼部过敏性疾病，如春季角结膜炎，不仅表现为结膜的过敏性炎症，包括 T 辅助 2 细胞和嗜酸性粒细胞浸润到结膜，还表现为各种角膜病变，如持续性上皮缺损和盾状溃疡。尽管角膜和结膜在眼部过敏性炎症中被认为相互影响，但体内这些组织之间相互作用的直接证据一直缺乏。嗜酸性粒细胞和嗜酸性粒细胞衍生的因子被认为与与眼部过敏相关的角膜病变的发病机制有关，在盾状溃疡中已经检测到来源于嗜酸性粒细胞的细胞毒性颗粒蛋白，如主要碱性蛋白和基质金属蛋白酶 9。主要碱性蛋白在培养的角膜上皮细胞中表现出细胞毒性作用，并抑制器官培养中的角膜上皮伤口愈合，而基质金属蛋白酶 9 可以降解角膜上皮基底膜。体外研究表明，细胞因子和其他炎症介质直接损害角膜上皮细胞的屏障功能，并增加角膜基质成纤维细胞中趋化因子和粘附分子的表达，这些作用可能增强过敏性炎症。我们最近表明，在眼部过敏的大鼠模型中，去除角膜上皮增强了迟发性临床体征和结膜嗜酸性粒细胞浸润，而结膜炎症则延迟了角膜上皮伤口愈合。因此，结膜过敏性炎症和角膜上皮紊乱在体内相互作用，形成恶性循环，中断这种循环可能为严重眼部过敏的治疗提供新的方法。
