Originally, miR-183C was identified as a sensory organ–enriched miRNA cluster.
30 It is highly expressed in all sensory neurons.
25,30,61,62 We and others have shown that miR-183C is required for normal vision,
25 hearing and balance,
25,63–66 olfaction,
64 touch, and mechanical and neuropathic pain.
67 We demonstrated that miR-183C plays an important role in neuroimmune interaction in the cornea.
24 Its inactivation in mice causes decreased corneal nerve density, reduced expression of TRPV1, disruption of the normal whorl-like pattern of the subbasal nerve plexus, and decreased expression of proinflammatory neuropeptides in the cornea, including
Tac1, the precursor gene for substance P (SP),
24 during disease resolution. SP is a chemoattractant and anti-apoptotic neuropeptide that enhances PMN infiltration and persistence in the cornea, the latter contributing to tissue damage and perforation.
28,37–41 Decreased neuropeptide expression, including SP, in the cornea of miR-183C knockout mice contributes to the decreased production of proinflammatory cytokines/chemokines and reduced severity of PA keratitis.
24 Consistent with these observations in the miR-183C knockout mice,
24 here we have shown that the application of anti-miR-183C to the cornea results in a transient and reversible reduction of corneal nerve density, with the whorl center of the subbasal nerve plexus being most affected. This may contribute to a decreased level of proinflammatory neuropeptide and neuroimmune/inflammatory responses in the cornea at a later stage of PA keratitis, similar to what was reported in miR-183C knockout mice.
24 The latter hypothesis is consistent with our observation of decreased IL-1β, reduced number of PMNs, and decreased severity of PA keratitis in anti-miR-183C versus NC ORN–treated mice. In the current study, to keep the uniformity of experimental condition, we used female C57BL/6 mice in the PA infection/prophylactic anti-miR treatment experiments. However, we are aware that, with new technological advances in science, sex-dependent differences have been reported in corneal nerves,
68 tissue resident immune cells, and innate immunity.
69–79 Therefore, we do not exclude the possibility that sex-dependent differences in the corneal response to PA infection upon anti-miR-183C treatment may exist. We will conduct such experiments in both male and females, separately, in future work.