Corneal epithelial and neuronal interactions: Role in nerve regeneration and wound healing

在角膜中，角膜上皮和三叉神经感觉神经末梢之间的持续通信对于上皮的正常功能是必不可少的。角膜神经支配和敏感性受损是角膜神经营养性角膜病的主要原因，同时也导致上皮伤口愈合不良。被破坏的神经末梢的再生和适当上皮的更新对于恢复角膜敏感性是必不可少的，并且在这种情况下，有必要在分子水平上研究角膜上皮和三叉神经元的相互作用，以阐明特定的个体分子及其在神经营养性角膜病期间在角膜伤口愈合和神经再生中的作用。在此之前，我们已经研究了角膜上皮细胞对三叉神经元的影响，以及三叉神经元对角膜上皮细胞在小鼠模型系统中的伤口愈合过程中的影响。我们观察到三叉神经感觉神经元中P物质（SP）mRNA表达的增加和其他细胞类型存在下角膜上皮细胞中骨形态发生蛋白7（BMP7）mRNA表达的减少。这项研究证实了角膜上皮细胞和三叉神经感觉神经元之间存在通讯，并为进一步研究这些分子在神经再生和伤口愈合过程中的作用开辟了新的维度。本研究旨在使用培养的原代人角膜上皮细胞和三叉神经元沿着研究SP和BMP 7对上皮和感觉神经元功能的影响，同时鉴定与伤口愈合和神经再生相关的新靶点。在SP和BMP 7的存在下，使用原代人细胞培养模型系统，剖析角膜伤口愈合和神经再生期间激活的信号传导途径的潜在机制，可以设计用于治疗眼部疾病的未来靶特异性治疗剂。

In the cornea, on-going communication between the corneal epithelium and trigeminal sensory nerve endings is indispensable for the proper functioning of the epithelium. Impaired corneal innervation and sensitivity are the main causes of corneal neurotrophic keratopathy which simultaneously also leads to poor epithelial wound healing. Regeneration of the disrupted nerve endings and renewal of the proper epithelium is essential to restore the corneal sensitivity and it is necessary, in this context, to investigate corneal epithelial and trigeminal neuron interactions at the molecular level to shed light on specific individual molecules and their role in corneal wound healing and nerve regeneration during neurotrophic keratopathy. Previously, we have studied the effect of corneal epithelial cells on trigeminal neurons as well as the effect of trigeminal neurons on corneal epithelial cells during wound healing in a murine model system. We observed an increase in the substance P (SP) mRNA expression in trigeminal sensory neurons and a decrease in the expression of bone morphogenetic protein 7 (BMP7) mRNA in corneal epithelial cells in the presence of the other cell-type. This study confirms the existence of communication between corneal epithelial cells and trigeminal sensory neurons and opens up new dimensions to further study the effect of these molecules during nerve regeneration and wound healing. Present study aims to study the effect of SP and BMP7 on epithelial and sensory neuron functions using cultured primary human corneal epithelial cells and trigeminal neurons along with identification of novel targets related to wound healing and nerve regeneration. Dissecting the underlying mechanisms of activated signaling pathways during corneal wound healing and nerve regeneration, using primary human cell culture model systems, in the presence of SP and BMP7 may enable designing of future target specific therapeutics for the treatment of ocular diseases.