Distribution of Corneal TRPV1 and Its Association With Immune Cells During Homeostasis and Injury

PURPOSE: Given the role of corneal sensory nerves during epithelial wound repair, we sought to examine the relationship between immune cells and polymodal nociceptors following corneal injury. METHODS: Young C57BL/6J mice received a 2 mm corneal epithelial injury. One week later, corneal wholemounts were immunostained using β-tubulin-488, TRPV1 (transient receptor potential ion channel subfamily V member-1, a nonselective cation channel) and immune cell (MHC-II, CD45 and CD68) antibodies. The sum length of TRPV1(+) and TRPV1(–) nerve fibers, and their spatial association with immune cells, was quantified in intact and injured corneas. RESULTS: TRPV1(+) nerves account for ∼40% of the nerve fiber length in the intact corneal epithelium and ∼80% in the stroma. In the superficial epithelial layers, TRPV1(+) nerve terminal length was similar in injured and intact corneas. In intact corneas, the density (sum length) of basal epithelial TRPV1(+) and TRPV1(−) nerve fibers was similar, however, in injured corneas, TRPV1(+) nerve density was higher compared to TRPV1(−) nerves. The degree of physical association between TRPV1(+) nerves and intraepithelial CD45(+) MHC-II(+) CD11c(+) cells was similar in intact and injured corneas. Stromal leukocytes co-expressed TRPV1, which was partially localized to CD68(+) lysosomes, and this expression pattern was lower in injured corneas. CONCLUSIONS: TRPV1(+) nerves accounted for a higher proportion of corneal nerves after injury, which may provide insights into the pathophysiology of neuropathic pain following corneal trauma. The close interactions of TRPV1(+) nerves with intraepithelial immune cells and expression of TRPV1 by stromal macrophages provide evidence of neuroimmune interactions in the cornea.