June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Mice with Desiccating Stress-Induced Dry Eye Develop Trigeminal Neuralgia, Despite Decreased Corneal Sensitivity and Nerve Fiber Degeneration
Author Affiliations & Notes
  • Chris Schaumburg
    Biological Sciences, Allergan, Irvine, CA
  • Katherine Held
    Biological Sciences, Allergan, Irvine, CA
  • Euikyun Oh
    Biological Sciences, Allergan, Irvine, CA
  • Sveti Ugarte
    Biological Sciences, Allergan, Irvine, CA
  • Larry Wheeler
    Biological Sciences, Allergan, Irvine, CA
  • Margarita Calonge
    IOBA, University of Valladolid, Valladolid, Spain
  • Jerry Niederkorn
    Ophthalmology, UT Southwestern Med Center, Dallas, TX
  • Stephen Pflugfelder
    Ophthalmology, Baylor College of Medicine, Houston, TX
  • Robert Fox
    Division of Reumatology, Scripps Memorial Hospital, Lo Jolla, CA
  • Michael Stern
    Biological Sciences, Allergan, Irvine, CA
  • Footnotes
    Commercial Relationships Chris Schaumburg, Allergan, Inc (E); Katherine Held, Allergan, Inc. (E); Euikyun Oh, Allergan, Inc (E); Sveti Ugarte, None; Larry Wheeler, Allergan Pharm (E); Margarita Calonge, Allergan (C); Jerry Niederkorn, Allergan (C); Stephen Pflugfelder, Allergan (C), Glaxo Smith Kline (C), Bausch and Lomb (C), Baylor College of Medicine (P); Robert Fox, None; Michael Stern, Allergan, Inc. (E)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 2194. doi:
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      Chris Schaumburg, Katherine Held, Euikyun Oh, Sveti Ugarte, Larry Wheeler, Margarita Calonge, Jerry Niederkorn, Stephen Pflugfelder, Robert Fox, Michael Stern; Mice with Desiccating Stress-Induced Dry Eye Develop Trigeminal Neuralgia, Despite Decreased Corneal Sensitivity and Nerve Fiber Degeneration. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2194.

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

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Abstract

Purpose: Pain is a major symptom of patients suffering from chronic Dry Eye disease. To begin to understand if the immunopathogenesis of desiccating stress (DS)-induced Dry Eye is associated with a pain response, corneal sensitivity, corneal nerve fiber density, neuropeptides and trigeminal neuralgia were evaluated over the course of disease.

Methods: Dry Eye disease was induced by exposing female C57BL/6 mice to desiccating stress (DS: subcutaneous scopolamine (1.0mg/0.2ml) TID; humidity <40%; sustained airflow). At various time points mice were evaluated for corneal sensitivity using von Frey filaments (Dixon up-down method), corneal nerve fibers with immunohistochemistry, neuropeptides using ELISA and trigeminal neuralgia with behavorial testing.

Results: IHC on flat mount whole corneas revealed a significant decrease (p<0.01) corneal nerve fiber density at Day 10, 15 and 20 of DS using neuronal class III beta-tubulin (Tuj1+) staining. Mice with Dry Eye disease also developed decreased corneal sensitivity very early, at Day 1 (0.21±0.10 gram force) and Day 3 (0.41±0.14 gram force; p=0.05) of DS compared to baseline (0.04±0.006 gram force). Mice with Dry Eye disease also developed robust trigeminal neuralgia by Day 15 (pain behavorial score = 4.67±.39 out of a maximum of 6.0; p<0.001), which was associated with upregulation of neuropeptides in the trigeminal ganglia; calcitonin gene related peptide (CGRP) and substance P were significantly (p=0.05) upregulated in the trigeminal ganglia by Day 15 of DS.

Conclusions: These data suggest that DS mice develop trigeminal neuralgia, despite decreased corneal sensitivity and nerve fiber degeneration during the progression of experimental Dry Eye disease.

Keywords: 486 cornea: tears/tear film/dry eye • 557 inflammation • 565 innervation: sensation  
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