TY - JOUR
T1 - Lacrimal gland denervation alters tear protein composition and impairs ipsilateral eye closures and corneal nociception
AU - Hegarty, Deborah M.
AU - David, Larry L.
AU - Aicher, Sue A.
N1 - Publisher Copyright:
© 2018 The Authors.
PY - 2018/10
Y1 - 2018/10
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.
KW - Dry eyes
KW - Pain
KW - Proteomics
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U2 - 10.1167/iovs.18-25267
DO - 10.1167/iovs.18-25267
M3 - Article
C2 - 30372750
AN - SCOPUS:85055618600
SN - 0146-0404
VL - 59
SP - 5217
EP - 5224
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
IS - 12
ER -