April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Nerve growth factor produces corneal hypersensitivity and increases menthol-induced tearing in the rat
Author Affiliations & Notes
  • Ian D Meng
    Biomedical Sciences, University of New England, Biddeford, ME
  • Stephen Barton
    Biomedical Sciences, University of New England, Biddeford, ME
  • Footnotes
    Commercial Relationships Ian Meng, None; Stephen Barton, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 1484. doi:
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      Ian D Meng, Stephen Barton; Nerve growth factor produces corneal hypersensitivity and increases menthol-induced tearing in the rat. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1484.

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Abstract

Purpose: Nerve growth factor (NGF) levels are increased in dry eye patients and NGF has been demonstrated to improve the rate of corneal wound healing. Clinical trials are currently in progress for recombinant human NGF and MIM-D3, a partial agonist to the NGF receptor TrkA, for the treatment of dry eye disease and corneal neurodegenerative diseases. The effects of NGF on corneal sensitivity are unknown, a surprising oversight since NGF has known proalgesic effects in other tissues and reducing NGF signaling is a strategy currently being pursued as a treatment for chronic pain. The purpose of the present study was to examine the effect of NGF applied to the cornea on mechanical sensitivity, nociceptive responses to the TRPV1 agonist capsaicin, and tearing elicited by the TRPM8 agonist menthol.

Methods: Corneal mechanical thresholds, capsaicin-evoked eye wipe behaviors, and menthol-induced tearing were measured 60 min after the application of NGF (200 µg/ml) to the eye in male SD rats. In addition, mechanical thresholds and eye wipe behaviors were examined after the chronic application of NGF (100 µg/ml, 2-times/day for 14 days). Tearing was quantified by inserting a phenol red cotton thread into the caudal corner of the eye for 30 s.

Results: Corneal mechanical thresholds were reduced and capsaicin-evoked eye-wipe behaviors were increased after both a single and repeated application of NGF to the cornea. In addition, menthol-induced tear secretion was increased 60 min after NGF application. Menthol did not induce eye wipe behaviors in NGF or vehicle treated animals.

Conclusions: These results indicate that NGF sensitizes corneal nociceptors to TRPV1 channel activation and mechanical stimuli. The increase in menthol-induced tearing in NGF treated animals may be due to the sensitization of corneal cold cells and provides additional rationale for current efforts targeting TrkA receptors as a treatment for dry eye disease.

Keywords: 486 cornea: tears/tear film/dry eye • 480 cornea: basic science • 765 wound healing  
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