Immunological interdependence between the two eyes has been reported for the cornea and the retina but not for the ocular mucosal surface. Intriguingly, patients frequently report ocular surface-related symptoms in the other eye after unilateral ocular surgery. Here we show how unilateral eye injuries in mice affect the mucosal immune response of the opposite ocular surface. We report that, despite the lack of lymphatic cross-drainage, a neurogenic inflammatory reflex in the contralateral conjunctiva is sufficient to increase, first, epithelial nuclear factor kappa B signaling, then, dendritic cell maturation, and finally, expansion of effector, instead of regulatory, T cells in the draining lymph node, leading to disrupted ocular mucosal tolerance. We also show that damage to ocular surface nerves is required. Using pharmacological inhibitors and agonists, we identified transient receptor potential vanilloid 1 (TRPV1) channel as the receptor sensing tissue damage in the injured eye and substance P released in the opposite ocular surface as the effector of the sympathetic response. Finally, blocking either step prevented subsequent ocular allergic reactions in the opposite eye in a unilateral corneal alkali burn model. This study demonstrates that both ocular surfaces are immunologically linked and suggests potential therapeutic targets for intervention.

中文翻译：

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双眼的粘膜表面通过涉及 TRPV1 和 P 物质的神经源性炎症反射在免疫学上相关联。

据报道，角膜和视网膜在两只眼睛之间存在免疫学相互依赖性，但眼粘膜表面却没有。有趣的是，患者在单侧眼部手术后经常报告另一只眼睛出现眼表相关症状。在这里，我们展示了小鼠单侧眼部损伤如何影响对侧眼表的粘膜免疫反应。我们报告说，尽管缺乏淋巴交叉引流，但对侧结膜中的神经源性炎症反射足以首先增加上皮核因子 kappa B 信号，然后增加树突细胞成熟，最后增加效应器的扩张，而不是引流淋巴结中的调节性 T 细胞，导致眼粘膜耐受性受损。我们还表明需要对眼表神经造成损害。使用药理抑制剂和激动剂，我们将瞬时受体电位香草素 1 (TRPV1) 通道确定为受伤眼中感受组织损伤的受体，并将在对侧眼表释放的 P 物质确定为交感神经反应的效应器。最后，在单侧角膜碱烧伤模型中，阻断任一步骤可防止对侧眼发生后续眼部过敏反应。这项研究表明，两个眼表都具有免疫相关性，并提出了潜在的干预治疗目标。在单侧角膜碱烧伤模型中，阻断任一步骤可防止对侧眼发生随后的眼部过敏反应。这项研究表明，两个眼表都具有免疫相关性，并提出了潜在的干预治疗目标。在单侧角膜碱烧伤模型中，阻断任一步骤可防止对侧眼发生随后的眼部过敏反应。这项研究表明，两个眼表都具有免疫相关性，并提出了潜在的干预治疗目标。