June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Neurokinin-1 Receptor Antagonism Ameliorates Ocular Pain and Immune Responses in Dry Eye Disease
Author Affiliations & Notes
  • Yukako Taketani
    Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, Massachusetts, United States
  • Amirreza Naderi
    Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, Massachusetts, United States
  • Shudan Wang
    Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, Massachusetts, United States
  • Tomas Blanco
    Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, Massachusetts, United States
  • Ann Yung
    Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, Massachusetts, United States
  • Jia Yin
    Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, Massachusetts, United States
  • Thomas Dohlman
    Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, Massachusetts, United States
  • Yihe Chen
    Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, Massachusetts, United States
  • Sunil Chauhan
    Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, Massachusetts, United States
  • Reza Dana
    Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Yukako Taketani, None; Amirreza Naderi, None; Shudan Wang, None; Tomas Blanco, None; Ann Yung, None; Jia Yin, None; Thomas Dohlman, None; Yihe Chen, Schepens Eye Research Institute (P); Sunil Chauhan, None; Reza Dana, Schepens Eye Research Institute (P)
  • Footnotes
    Support  National Eye Institute/National Institutes of Health grant R01EY020889
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 1286. doi:
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      Yukako Taketani, Amirreza Naderi, Shudan Wang, Tomas Blanco, Ann Yung, Jia Yin, Thomas Dohlman, Yihe Chen, Sunil Chauhan, Reza Dana; Neurokinin-1 Receptor Antagonism Ameliorates Ocular Pain and Immune Responses in Dry Eye Disease. Invest. Ophthalmol. Vis. Sci. 2021;62(8):1286.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Ocular pain is a common symptom of dry eye disease (DED). Our previous work has demonstrated increased levels of the neuropeptide substance P (SP) in DED. SP preferentially activates the neurokinin 1 receptor (NK1R) to mediate an inflammatory response. However, the direct effects of SP in ocular pain in DED are unknown. The purpose of this study was to determine the contributions of SP to ocular pain and inflammation in DED through antagonism of NK1R.

Methods : DED was induced in 6 week old C57BL/6 female mice by housing them in a controlled environment chamber for 14 days. Eye wiping test was performed to evaluate pain after instillation of hypertonic saline (2M NaCl) on days 0, 2, 4, 7, 10, and 14 during DED induction. L-733,060 (1μg/μl), an NK1R antagonist, was administered topically twice per day from day 0 to day 14 after DED induction. Cornea, draining lymph nodes (dLNs), and trigeminal nerve ganglion (TG) were collected on day 14. SP expression in TG and cornea were measured by ELISA. The frequency of MHC-IIhighCD11b+ cells in dLNs was assessed using flow cytometry.

Results : Eye wipe behavior was significantly increased in the DED group compared to the normal group (P < 0.001) and the peak was reached on day 4 (P = 0.02). Application of L-733,060 to DED mice led to significantly decreased eye wipe behavior at day 4 and 14 (P = 0.03). Corneal SP expression levels were 25% lower in the L-733,060 group compared to the untreated DED group (724±24pg/100μg vs. 976±82pg/100μg, P = 0.051) at day 14. In the TG, no difference in SP level was observed amongst groups (P = 0.97). Additionally, the L-733,060 group showed significantly fewer MHC-IIhighCD11b+cells compared to the untreated DED group at day 14 (2.82±0.26% vs. 4.46± 0.24%, P = 0.001).

Conclusions : Our data demonstrate that antagonism of NK1R simultaneously reduces ocular pain and suppresses inflammation in a murine model of DED, suggesting SP blockade as a new therapeutic strategy in the management of DED.

This is a 2021 ARVO Annual Meeting abstract.

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