Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
Commun Biol. 2024 Mar 4;7(1):264. doi: 10.1038/s42003-024-05934-y.
Calcitonin gene-related peptide (CGRP) is a multifunctional neuropeptide abundantly expressed by corneal nerves. Using a murine model of corneal mechanical injury, we found CGRP levels in the cornea significantly reduced after injury. Topical application of CGRP as an eye drop accelerates corneal epithelial wound closure, reduces corneal opacification, and prevents corneal edema after injury in vivo. CGRP promotes corneal epithelial cell migration, proliferation, and the secretion of laminin. It reduces TGF-β1 signaling and prevents TGF-β1-mediated stromal fibroblast activation and tissue fibrosis. CGRP preserves corneal endothelial cell density, morphology, and pump function, thus reducing corneal edema. Lastly, CGRP reduces neutrophil infiltration, macrophage maturation, and the production of inflammatory cytokines in the cornea. Taken together, our results show that corneal nerve-derived CGRP plays a cytoprotective, pro-regenerative, anti-fibrotic, and anti-inflammatory role in corneal wound healing. In addition, our results highlight the critical role of sensory nerves in ocular surface homeostasis and injury repair.
降钙素基因相关肽（CGRP）是一种丰富表达于角膜神经的多功能神经肽。我们通过小鼠角膜机械损伤模型发现，损伤后角膜中的 CGRP 水平显著降低。局部应用 CGRP 滴眼剂可加速角膜上皮伤口愈合，减少角膜混浊，并预防损伤后的角膜水肿。CGRP 促进角膜上皮细胞迁移、增殖和层粘连蛋白的分泌。它减少 TGF-β1 信号转导，并防止 TGF-β1 介导的基质成纤维细胞激活和组织纤维化。CGRP 可维持角膜内皮细胞密度、形态和泵功能，从而减少角膜水肿。最后，CGRP 减少了角膜中的中性粒细胞浸润、巨噬细胞成熟和炎症细胞因子的产生。综上所述，我们的研究结果表明，角膜神经源性 CGRP 在角膜伤口愈合中发挥细胞保护、促进再生、抗纤维化和抗炎作用。此外，我们的研究结果强调了感觉神经在眼表面稳态和损伤修复中的关键作用。
