July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Inhibition of corneal nociceptors reduces persistent, ongoing dry eye-induced pain
Author Affiliations & Notes
  • Neal Mecum
    Center for Excellence in Neuroscience, University of New England, Biddeford, Maine, United States
    University of Maine, Orono, Maine, United States
  • Rachel Russell
    Center for Excellence in Neuroscience, University of New England, Biddeford, Maine, United States
  • Joshua Havelin
    Center for Excellence in Neuroscience, University of New England, Biddeford, Maine, United States
    University of Maine, Orono, Maine, United States
  • Ian Meng
    Center for Excellence in Neuroscience, University of New England, Biddeford, Maine, United States
    College of Osteopathic Medicine, University of New England, Biddeford, Maine, United States
  • Footnotes
    Commercial Relationships   Neal Mecum, None; Rachel Russell, None; Joshua Havelin, None; Ian Meng, None
  • Footnotes
    Support  R01EY026145 and COBRE P20GM103643
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 311. doi:
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      Neal Mecum, Rachel Russell, Joshua Havelin, Ian Meng; Inhibition of corneal nociceptors reduces persistent, ongoing dry eye-induced pain. Invest. Ophthalmol. Vis. Sci. 2019;60(9):311.

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

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Abstract

Purpose :
Previously, we have shown that lacrimal gland excision (LGE)-induced dry eye decreases corneal afferent innervation and increases corneal sensitivity to mechanical and chemical stimuli. In addition, LGE produced an increase in blink rate (rats) or squinting (mice) behavior, suggesting the presence of persistent ongoing pain. The aim of the present study was to investigate the presence of ongoing pain by studying real-time place preference induced by inhibition of Nav1.8 expressing corneal afferent neurons following LGE.

Methods :
The proton pump archaerhodopsin-3/EGFP (ArchT/EGFP) was conditionally expressed in corneal afferents using Nav1.8-cre mice. Dry eye was produced by a unilateral LGE, with sham surgery used as a control. Eye closure (squinting) was measured using a ratio consisting of the height of the gap between the upper and lower eyelids and the distance separating the two canthi. Real time place preference was assessed using a 3-chamber apparatus. A neutral center chamber was flanked by one illuminated with a control light source (wavelength=360-400nm) and one illuminated with an ArchT-activating light (560-610nm). Animals were placed in the neutral chamber and movement was tracked over three 10 min sessions, with the lights turned on only during the second session. Co-administration of the topical anesthetic lidocaine N-ethyl bromide (QX-314, 0.5% w/v) and lidocaine (2% w/v) was used to examine the role of corneal afferents in producing squinting behavior and real time place preference.

Results :
After LGE, ArchT/EGFP/Nav1.8-cre mice showed a significant real-time place preference for the chamber illuminated with ArchT activating light. This effect was long lasting, as animals continued to prefer the chamber even after the light turned off during the third session. No effect of the light was observed in animals with sham surgery or in wild-type animals following LGE. In addition, topical application of QX-314 + lidocaine returned eye closure ratios to sham levels, with an effect lasting for 1hr.

Conclusions :
These results indicate that LGE produces persistent, ongoing pain driven by Nav1.8 expressing corneal afferents. Inhibition of these neurons is a potential strategy for treating the ongoing irritation and pain associated with chronic dry eye.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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