Fig. 8: Model showing how TRPV1⁺ sensory nerves modulate corneal inflammation after corneal injury.

Based on this study and other data, we hypothesize that corneal abrasions activate TRPV1⁺ sensory nerve endings in the cornea to release the neuropeptides SST and CGRP, which reduce the degree of inflammatory response to corneal injury by binding to corresponding receptors expressed in different preferential ways on each of the three immune cell types. For neutrophils, the SST released from TRPV1⁺ nerve terminals acts directly on neutrophils via the SST-SSTR5 axis to inhibit their recruitment to the injured cornea. As for γδ T cells, both the CGRP and SST released from TRPV1⁺ nerve endings inhibited their infiltration and expression of the pro-inflammatory cytokines TNF-α and IL-17A via both the CGRP-RAMP1 and SST-SSTR5 pathways, thereby indirectly dampening neutrophil recruitment. Notably, for the two different macrophage populations in the cornea, TRPV1⁺ sensory nerves then regulate the local inflammatory response through two different mechanisms. In the case of CCR2⁺ macrophages, the CGRP from the nerve terminal inhibits their accumulation in the wounded cornea and production of the pro-inflammatory cytokine TNF-α by binding to the corresponding receptor RAMP1 on the macrophages. However, for CCR2^‒ macrophages, the SST released from nerve terminals promotes their recruitment to the injured cornea and production of the immunosuppressive cytokine IL-10 by binding to the macrophage-expressed receptor SSTR5. Ultimately, TRPV1 + sensory nerves control the inflammatory response process after corneal trauma to an appropriate level through the direct and indirect action of released neuropeptides on different immune cells and the interaction between different immune cells.