September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Short exposure to hyperosmolar tears produces profound anatomical and physiological changes in rodent corneal nerves: Implications for dry eye disease.
Author Affiliations & Notes
  • Kamila K Mizerska
    Department of Ophthalmology, Dyson Vision Research Institute, Weill Cornell Medical College, New York, New York, United States
  • Harumitsu Hirata
    Department of Ophthalmology, Dyson Vision Research Institute, Weill Cornell Medical College, New York, New York, United States
  • Valentina Dallacasagrande
    Department of Ophthalmology, Dyson Vision Research Institute, Weill Cornell Medical College, New York, New York, United States
  • Carl F Marfurt
    Department of Anatomy and Cell Biology, Indiana University School of Medicine-Northwest, Gary, Indiana, United States
  • Mark Rosenblatt
    Department of Ophthalmology and Visual Science, University of Illinois College of Medicine, Chicago, Illinois, United States
  • Footnotes
    Commercial Relationships   Kamila Mizerska, None; Harumitsu Hirata, None; Valentina Dallacasagrande, None; Carl Marfurt, None; Mark Rosenblatt, None
  • Footnotes
    Support  NIH Grants EY023555 (HH), EY018594 (MIR), and the Research to Prevent Blindness Grants to Department of Ophthalmology, Weill Cornell Medical College.
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 403. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Kamila K Mizerska, Harumitsu Hirata, Valentina Dallacasagrande, Carl F Marfurt, Mark Rosenblatt; Short exposure to hyperosmolar tears produces profound anatomical and physiological changes in rodent corneal nerves: Implications for dry eye disease.
      . Invest. Ophthalmol. Vis. Sci. 2016;57(12):403.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Hyperosmolar tears and corneal nerve abnormalities are frequently observed in dry eye patients; however, these two phenomena have not been systematically studied together. The purpose of this study was to investigate the relationship between tear hyperosmolarity and corneal nerve abnormalities in an effort to explain signs and symptoms of dry eye disease.

Methods : Immunohistochemistry: The left and right eyes of rats and mice were treated with hyperosmolar tear solutions (HOS; 600-1000 mOsm NaCl or mannitol) or artificial tears (ATs), respectively, for 30 min to 3 hrs. Then, the morphology of the corneal epithelial innervation was evaluated by staining corneal whole mounts with antisera against the pan-neuronal marker neurotubulin. Electrophysiology: Single corneal neurons were recorded extracellularly from rat trigeminal ganglia. The neuronal responses to corneal drying (an important stimulus for tearing) were noted before, and 30 min, 1hr, and 3hrs after, continuous ocular application of HOS (450-1000 mOsm).

Results : Immunohistochemistry: In contrast to ATs-treated corneas, HOS-treated corneas contained numerous subbasal nerve fibers (SNFs) that were morphologically abnormal, the degree of which appeared to be dose- and time-dependent. The most severely affected SNFs exhibited signs of degeneration; the fibers were fragmented and appeared as linear arrays of non-interconnected beads. In contrast, intraepithelial terminals in ATs -and HOS-treated corneas were morphologically indistinguishable, appeared anatomically intact, and exhibited no signs of HOS-induced degeneration. Electrophysiology: The responses of corneal neurons to drying of the cornea were depressed or even completely abolished by hyperosmolar tears in a time- and dose-dependent manner. The disappearance of action potentials occurred as quickly as 2 min, but generally within 3 hrs, after HOS application.

Conclusions : These results demonstrate for the first time that exposure of the corneal surface to hyperosmotic tears causes considerable damages to corneal SNFs that are consistent with the abnormal activities of trigeminal ganglion neurons demonstrated by electrophysiological recordings. These observations may account for the signs (morphological abnormalities) and symptoms (abnormal sensations) reported in dry eye patients.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×