Abstract
Purpose :
Among the various inflammatory mechanisms involved in dry eye disease (DED), mechanisms of neurogenic inflammation remain largely unexplored. The aim of this study was to elucidate the involvement of transient receptor potential ankyrin-1 (TRPA1) corneal nociceptors in trigeminal neurogenic inflammation associated with persistent DED.
Methods :
DED was induced in adult male C57BL6J mice by the unilateral removal of the Harderian and extra orbital lacrimal glands. Mice were split in two groups: DED mice treated with TRPA1 antagonist (HC030031, 100µM) or with vehicle (PBS). Both treatments were topically administrated in the operated eye twice a day for 2 weeks from D7 to D21 after surgery. Ipsilateral trigeminal ganglia (TG) were collected and mRNA expressions of neuropeptides, and inflammatory chemokines/cytokines were evaluated.
Results :
The expression of TRPA1 in TG was significantly decreased in DED mice treated with TRPA1 antagonist compared to DED mice treated with vehicle (Mann-Whitney test, p-value<0.05). Interestingly, the expressions of TRPV1, NAV1.8 and NAV1.9 were significantly increased in TG of DED mice treated with the TRPA1 antagonist compared to DED mice treated with vehicle (Mann-Whitney test, p-value<0.05). Also, CGRP and SP were significantly less expressed in TG of DED mice treated with TRPA1 antagonist compared to DED mice treated with vehicle (Mann-Whitney test, p-value<0.05). Furthermore, expressions of inflammatory cytokines (IL6, IL1β) and chemokines (CCL12, CCR2) were significantly decreased in TG of DED mice treated with the TRPA1 antagonist compared to DED mice treated with vehicle (Mann-Whitney test, p-value<0.05).
Conclusions :
Our results indicated that inhibition of TRPA1 corneal nociceptors in DED mice leads to a decreased expression of TRPA1, of neuropeptides related to neurogenic inflammation (CGRP, SP) and of inflammatory cytokines/chemokines (IL6, IL1β, CCL12, CCR2) in mice TG. Together, our results suggest that TRPA1 corneal nociceptors are important regulators of trigeminal neurogenic inflammation.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.