Lacrimal Gland Denervation Alters Tear Protein Composition and Impairs Ipsilateral Eye Closures and Corneal Nociception

Deborah M. Hegarty, Larry David, Sue Aicher

Research output: Contribution to journalArticle

Abstract

Purpose: To evaluate spontaneous and evoked ocular sensory responses in rats after denervation of the lacrimal gland, as well as protein changes in tears that may mediate functional changes.

Methods: Sprague-Dawley rats served as subjects. The left lacrimal gland was partially denervated with saporin toxin conjugated to p75. Unilateral and bilateral eye closures (winks and blinks) and grooming behaviors were measured weekly. Nociceptive responses were evoked by ocular application of menthol; tear production was assessed using the phenol thread test. Relative changes in tear protein abundances were measured using a Tandem Mass Tagging approach.

Results: Denervation of the lacrimal gland reduced eye closure behavior, particularly in the ipsilateral eye, and eye wipe responses to noxious menthol were also reduced. Tear volume did not change, but tear protein composition was altered. Proteins implicated in the structural integrity of epithelial cells and in protective functions were reduced by lacrimal denervation, including keratins, serotransferrin, and beta-defensin. Other proteins that may modulate TRPM8 channels and alter sensory neuronal function were reduced, including arachidonate 15-lipoxygenase B. A low-abundance protein that responds to oxidative stress and injury, proteasome subunit beta type 10, was upregulated in denervated rats.

Conclusions: Denervation of the lacrimal gland causes long-lasting hypoalgesia, impairs the blink response, and alters tear proteins. Tear proteins were altered without changing tear volume. We speculate that impaired TRPM8 function in corneal sensory nerves may contribute to ocular hypoalgesia, supporting growing evidence that this transduction molecule is important for both nociceptive and spontaneous blinking behaviors.

Original languageEnglish (US)
Pages (from-to)5217-5224
Number of pages8
JournalInvestigative ophthalmology & visual science
Volume59
Issue number12
DOIs
StatePublished - Oct 1 2018

Fingerprint

Lacrimal Apparatus
Nociception
Denervation
Tears
Menthol
Proteins
Arachidonate 15-Lipoxygenase
beta-Defensins
Blinking
Grooming
Proteasome Endopeptidase Complex
Transferrin
Keratins
Phenol
tear proteins
Sprague Dawley Rats
Oxidative Stress
Epithelial Cells
Wounds and Injuries

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

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title = "Lacrimal Gland Denervation Alters Tear Protein Composition and Impairs Ipsilateral Eye Closures and Corneal Nociception",
abstract = "Purpose: To evaluate spontaneous and evoked ocular sensory responses in rats after denervation of the lacrimal gland, as well as protein changes in tears that may mediate functional changes.Methods: Sprague-Dawley rats served as subjects. The left lacrimal gland was partially denervated with saporin toxin conjugated to p75. Unilateral and bilateral eye closures (winks and blinks) and grooming behaviors were measured weekly. Nociceptive responses were evoked by ocular application of menthol; tear production was assessed using the phenol thread test. Relative changes in tear protein abundances were measured using a Tandem Mass Tagging approach.Results: Denervation of the lacrimal gland reduced eye closure behavior, particularly in the ipsilateral eye, and eye wipe responses to noxious menthol were also reduced. Tear volume did not change, but tear protein composition was altered. Proteins implicated in the structural integrity of epithelial cells and in protective functions were reduced by lacrimal denervation, including keratins, serotransferrin, and beta-defensin. Other proteins that may modulate TRPM8 channels and alter sensory neuronal function were reduced, including arachidonate 15-lipoxygenase B. A low-abundance protein that responds to oxidative stress and injury, proteasome subunit beta type 10, was upregulated in denervated rats.Conclusions: Denervation of the lacrimal gland causes long-lasting hypoalgesia, impairs the blink response, and alters tear proteins. Tear proteins were altered without changing tear volume. We speculate that impaired TRPM8 function in corneal sensory nerves may contribute to ocular hypoalgesia, supporting growing evidence that this transduction molecule is important for both nociceptive and spontaneous blinking behaviors.",
author = "Hegarty, {Deborah M.} and Larry David and Sue Aicher",
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T1 - Lacrimal Gland Denervation Alters Tear Protein Composition and Impairs Ipsilateral Eye Closures and Corneal Nociception

AU - Hegarty, Deborah M.

AU - David, Larry

AU - Aicher, Sue

PY - 2018/10/1

Y1 - 2018/10/1

N2 - Purpose: To evaluate spontaneous and evoked ocular sensory responses in rats after denervation of the lacrimal gland, as well as protein changes in tears that may mediate functional changes.Methods: Sprague-Dawley rats served as subjects. The left lacrimal gland was partially denervated with saporin toxin conjugated to p75. Unilateral and bilateral eye closures (winks and blinks) and grooming behaviors were measured weekly. Nociceptive responses were evoked by ocular application of menthol; tear production was assessed using the phenol thread test. Relative changes in tear protein abundances were measured using a Tandem Mass Tagging approach.Results: Denervation of the lacrimal gland reduced eye closure behavior, particularly in the ipsilateral eye, and eye wipe responses to noxious menthol were also reduced. Tear volume did not change, but tear protein composition was altered. Proteins implicated in the structural integrity of epithelial cells and in protective functions were reduced by lacrimal denervation, including keratins, serotransferrin, and beta-defensin. Other proteins that may modulate TRPM8 channels and alter sensory neuronal function were reduced, including arachidonate 15-lipoxygenase B. A low-abundance protein that responds to oxidative stress and injury, proteasome subunit beta type 10, was upregulated in denervated rats.Conclusions: Denervation of the lacrimal gland causes long-lasting hypoalgesia, impairs the blink response, and alters tear proteins. Tear proteins were altered without changing tear volume. We speculate that impaired TRPM8 function in corneal sensory nerves may contribute to ocular hypoalgesia, supporting growing evidence that this transduction molecule is important for both nociceptive and spontaneous blinking behaviors.

AB - Purpose: To evaluate spontaneous and evoked ocular sensory responses in rats after denervation of the lacrimal gland, as well as protein changes in tears that may mediate functional changes.Methods: Sprague-Dawley rats served as subjects. The left lacrimal gland was partially denervated with saporin toxin conjugated to p75. Unilateral and bilateral eye closures (winks and blinks) and grooming behaviors were measured weekly. Nociceptive responses were evoked by ocular application of menthol; tear production was assessed using the phenol thread test. Relative changes in tear protein abundances were measured using a Tandem Mass Tagging approach.Results: Denervation of the lacrimal gland reduced eye closure behavior, particularly in the ipsilateral eye, and eye wipe responses to noxious menthol were also reduced. Tear volume did not change, but tear protein composition was altered. Proteins implicated in the structural integrity of epithelial cells and in protective functions were reduced by lacrimal denervation, including keratins, serotransferrin, and beta-defensin. Other proteins that may modulate TRPM8 channels and alter sensory neuronal function were reduced, including arachidonate 15-lipoxygenase B. A low-abundance protein that responds to oxidative stress and injury, proteasome subunit beta type 10, was upregulated in denervated rats.Conclusions: Denervation of the lacrimal gland causes long-lasting hypoalgesia, impairs the blink response, and alters tear proteins. Tear proteins were altered without changing tear volume. We speculate that impaired TRPM8 function in corneal sensory nerves may contribute to ocular hypoalgesia, supporting growing evidence that this transduction molecule is important for both nociceptive and spontaneous blinking behaviors.

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