Neuroscience Center of Excellence, School of Medicine, Louisiana State University Health New Orleans, New Orleans, LA, 70112, USA.
Sci Rep. 2020 Mar 12;10(1):4582. doi: 10.1038/s41598-020-61390-8.
The high-density corneal innervation plays a pivotal role in sustaining the integrity of the ocular surface. We have previously demonstrated that pigment epithelium-derived factor (PEDF) plus docosahexaenoic acid (DHA) promotes corneal nerve regeneration; here, we report the mechanism involved and the discovery of a stereospecific Resolvin D6-isomer (RvD6si) that drives the process. RvD6si promotes corneal wound healing and functional recovery by restoring corneal innervation after injury. RvD6si applied to the eye surface elicits a specific transcriptome signature in the trigeminal ganglion (TG) that includes Rictor, the rapamycin-insensitive complex-2 of mTOR (mTORC2), and genes involved in axon growth, whereas genes related to neuropathic pain are decreased. As a result, attenuation of ocular neuropathic pain and dry eye will take place. Thus, RvD6si opens up new therapeutic avenues for pathologies that affect corneal innervation.
高密度角膜神经支配在维持眼表面完整性方面起着关键作用。我们之前已经证明，色素上皮衍生因子（PEDF）加二十二碳六烯酸（DHA）可促进角膜神经再生；在这里，我们报告了所涉及的机制以及立体特异性 Resolvin D6-异构体（RvD6si）的发现，该异构体可驱动该过程。RvD6si 通过在损伤后恢复角膜神经支配来促进角膜伤口愈合和功能恢复。RvD6si 施用于眼表面会在三叉神经节（TG）中引发特定的转录组特征，其中包括雷帕霉素不敏感复合物-2 的 mTOR（mTORC2）和参与轴突生长的基因，而与神经病理性疼痛相关的基因则减少。结果，眼神经性疼痛和干眼症会得到缓解。因此，RvD6si 为影响角膜神经支配的病理开辟了新的治疗途径。
