Timely initiation and termination of inflammatory response after corneal epithelial abrasion is critical for the recovery of vision. The cornea is innervated with rich sensory nerves with highly dense TRPV1 nociceptors. However, the roles of TRPV1+ sensory neurons in corneal inflammation after epithelial abrasion are not completely understood. Here, we found that depletion of TRPV1+ sensory nerves using resiniferatoxin (RTX) and blockade of TRPV1 using AMG-517 delayed corneal wound closure and enhanced the infiltration of neutrophils and γδ T cells to the wounded cornea after epithelial abrasion. Furthermore, depletion of TRPV1+ sensory nerves increased the number and TNF-α production of corneal CCR2+ macrophages and decreased the number of corneal CCR2– macrophages and IL-10 production. In addition, the TRPV1+ sensory nerves inhibited the recruitment of neutrophils and γδ T cells to the cornea via RAMP1 and SSTR5 signaling, decreased the responses of CCR2+ macrophages via RAMP1 signaling, and increased the responses of CCR2– macrophages via SSTR5 signaling. Collectively, our results suggest that the TRPV1+ sensory nerves suppress inflammation to support corneal wound healing via RAMP1 and SSTR5 signaling, revealing potential approaches for improving defective corneal wound healing in patients with sensory neuropathy.
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This work was supported by the National Natural Science Foundation of China through Grants 82171014 (to Z.L.), 32100715 (to J.L.), and 81770962 (to Z.L.), the Science and Technology Program of Guangzhou of China through Grant 202102020002 (to J.L.), and the PhD Start-up Fund of the Natural Science Foundation of Guangdong Province of China through Grant 2018A030310605 (to J.L.).
The authors declare no competing interests.
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Liu, J., Huang, S., Yu, R. et al. TRPV1+ sensory nerves modulate corneal inflammation after epithelial abrasion via RAMP1 and SSTR5 signaling. Mucosal Immunol 15, 867–881 (2022). https://doi.org/10.1038/s41385-022-00533-8