Denervation of the lacrimal gland leads to corneal hypoalgesia in a novel rat model of aqueous dry eye disease

Sue A. Aicher, Sam M. Hermes, Deborah M. Hegarty

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


PURPOSE. Some dry eye disease (DED) patients have sensitized responses to corneal stimulation, while others experience hypoalgesia. Many patients have normal tear production, suggesting that reduced tears are not always the cause of DED sensory dysfunction. In this study, we show that disruption of lacrimal innervation can produce hypoalgesia without changing basal tear production. METHODS. Injection of a saporin toxin conjugate into the extraorbital lacrimal gland of male Sprague-Dawley rats was used to disrupt cholinergic innervation to the gland. Tear production was assessed by phenol thread test. Corneal sensory responses to noxious stimuli were assessed using eye wipe behavior. Saporin DED animals were compared to animals treated with atropine to produce aqueous DED. RESULTS. Cholinergic innervation and acetylcholine content of the lacrimal gland were significantly reduced in saporin DED animals, yet basal tear production was normal. Saporin DED animals demonstrated normal eye wipe responses to corneal application of capsaicin, but showed hypoalgesia to corneal menthol. Corneal nerve fiber density was normal in saporin DED animals. Atropine-treated animals had reduced tear production but normal responses to ocular stimuli. CONCLUSIONS. Because only menthol responses were impaired, cold-sensitive corneal afferents appear to be selectively altered in our saporin DED model. Hypoalgesia is not due to reduced tear production, since we did not observe hypoalgesia in an atropine DED model. Corneal fiber density is unaltered in saporin DED animals, suggesting that molecular mechanisms of nociceptive signaling may be impaired. The saporin DED model will be useful for exploring the mechanism underlying corneal hypoalgesia.

Original languageEnglish (US)
Pages (from-to)6981-6989
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Issue number11
StatePublished - Oct 1 2015


  • Cholinergic fibers
  • Corneal sensitivity
  • Dry eye disease
  • Saporin toxin
  • Sensory responses

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


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