March 2012
Volume 53, Issue 14
ARVO Annual Meeting Abstract  |   March 2012
Tear hyperosmolarity is a key predictor of the ocular dryness-evoked corneal afferent activity implicated in tear production: Significance to Dry Eye Disease
Author Affiliations & Notes
  • Harumitsu Hirata
    Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania
  • Michael Oshinsky
    Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania
  • Footnotes
    Commercial Relationships  Harumitsu Hirata, None; Michael Oshinsky, None
  • Footnotes
    Support  NIH Grant EY020667
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 2703. doi:
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      Harumitsu Hirata, Michael Oshinsky; Tear hyperosmolarity is a key predictor of the ocular dryness-evoked corneal afferent activity implicated in tear production: Significance to Dry Eye Disease. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2703.

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

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Purpose: : Tear hyperosmolarity is a ubiquitous sign observed in patients with dry eye disease (DED). Our previous studies implicated the special types of corneal afferents in the production of the basal tears. These afferents show novel sensitivity to the ocular dryness, a stimulus thought to be important in lacrimation. This study assesses which physiological stimuli, cooling and/or hyperosmolar stimulus, underlie the response to ocular dryness, and to speculate on their roles in the development of DED.

Methods: : Single sensory neurons innervating the cornea that respond to ocular dryness were recorded in vivo extracellularly from the trigeminal ganglion of isoflurane-anesthetized rats with tungsten microelectrodes. The neurons were subjected to ocular stimuli previously found to alter the activity of these neurons, such as ocular dryness, wetness, cooling (11oC change from 31oC adapting temperature), and hyperosmolar stimuli (585 mOsm).

Results: : 1) The pattern of activity during drying of the cornea was similar to the sustained responses observed during the hyperosmolar stimulus applied to the ocular surface. This was particularly evident for the neurons that lack a cooling sensitivity. 2) The dry responses in the neurons with exquisite sensitivity to cooling were more highly correlated with the cooling threshold and the magnitudes of cool response than the responses to the hyperosmolar stimulus. 3) The neurons with high sensitivity to hyperosmolar stimulus had low sensitivity to cooling, and vice versa. 4) The responses to the TRPM8 antagonist, BCTC, were similar for both dryness- and hyperosmolar stimulus-evoked activity.

Conclusions: : The cooling and hyperosmolar stimulation of the ocular surface differentially contribute to the ocular dryness-evoked activation of the corneal afferents implicated in tearing, depending on the neuronal types. The importance of the hyperosmolar stimulus in activating these afferents was especially apparent for a particular class of neurons, which displayed virtually no temperature sensitivity yet produced vigorous discharges in responses to ocular dryness and hyperosmolar stimulation of the cornea. The dysfunction of these neurons may lead to diminished tear production by hyperosmolar tears, creating the vicious cycle seen in dry eye patients.

Keywords: cornea: basic science • cornea: tears/tear film/dry eye • electrophysiology: non-clinical 

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