Department of Optometry and Vision Sciences, The University of Melbourne, Parkville, Victoria, Australia.
School of Biomedical Sciences, Institute of Clinical Sciences, University of Birmingham, Birmingham, United Kingdom, B15 2TT, United Kingdom.
Prog Retin Eye Res. 2022 Nov;91:101105. doi: 10.1016/j.preteyeres.2022.101105. Epub 2022 Jul 19.
In the cornea, resident immune cells are in close proximity to sensory nerves, consistent with their important roles in the maintenance of nerves in both homeostasis and inflammation. Using in vivo confocal microscopy in humans, and ex vivo immunostaining and fluorescent reporter mice to visualize corneal sensory nerves and immune cells, remarkable progress has been made to advance our understanding of the physical and functional interactions between corneal nerves and immune cells. In this review, we summarize and discuss recent studies relating to corneal immune cells and sensory nerves, and their interactions in health and disease. In particular, we consider how disrupted corneal nerve axons can induce immune cell activity, including in dendritic cells, macrophages and other infiltrating cells, directly and/or indirectly by releasing neuropeptides such as substance P and calcitonin gene-related peptide. We summarize growing evidence that the role of corneal intraepithelial immune cells is likely different in corneal wound healing versus other inflammatory-dominated conditions. The role of different types of macrophages is also discussed, including how stromal macrophages with anti-inflammatory phenotypes communicate with corneal nerves to provide neuroprotection, while macrophages with pro-inflammatory phenotypes, along with other infiltrating cells including neutrophils and CD4 T cells, can be inhibitory to corneal re-innervation. Finally, this review considers the bidirectional interactions between corneal immune cells and corneal nerves, and how leveraging this interaction could represent a potential therapeutic approach for corneal neuropathy.
在角膜中，常驻免疫细胞与感觉神经非常接近，这与它们在维持神经的稳态和炎症中的重要作用一致。通过在人体中使用共聚焦显微镜，以及在体外免疫染色和荧光报告小鼠中可视化角膜感觉神经和免疫细胞，在推进我们对角膜神经和免疫细胞之间的物理和功能相互作用的理解方面取得了显著进展。在这篇综述中，我们总结和讨论了与角膜免疫细胞和感觉神经及其在健康和疾病中的相互作用相关的最近研究。特别是，我们考虑了角膜神经轴突的破坏如何直接和/或间接通过释放 P 物质和降钙素基因相关肽等神经肽来诱导免疫细胞活性，包括树突状细胞、巨噬细胞和其他浸润细胞。我们总结了越来越多的证据表明，角膜上皮内免疫细胞在角膜伤口愈合与其他以炎症为主导的情况下的作用可能不同。还讨论了不同类型的巨噬细胞的作用，包括具有抗炎表型的基质巨噬细胞如何与角膜神经通讯以提供神经保护，而具有促炎表型的巨噬细胞以及其他浸润细胞，包括中性粒细胞和 CD4 T 细胞，可能对角膜再神经支配具有抑制作用。最后，本综述考虑了角膜免疫细胞和角膜神经之间的双向相互作用，以及利用这种相互作用如何成为治疗角膜神经病的潜在治疗方法。
