July 2018
Volume 59, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2018
Thirty-minute ocular application of benzalkonium chloride (BAK) leads to a disappearance of neuronal spikes associated with a marked fragmentation of tight junctions and corneal nerves in rodents: implications for dry eye disease.
Author Affiliations & Notes
  • Evguenia Ivakhnitskaia
    Ophthalmology and Visual Sciences, University of Illinois-Chicago, Chicago, Illinois, United States
  • Kamila Mizerska
    Ophthalmology, Weill Cornell Medical College, New York City, New York, United States
  • Valentina Dallacasagrande
    Ophthalmology, Weill Cornell Medical College, New York City, New York, United States
  • Victor H Guaiquil
    Ophthalmology and Visual Sciences, University of Illinois-Chicago, Chicago, Illinois, United States
  • Mark Rosenblatt
    Ophthalmology and Visual Sciences, University of Illinois-Chicago, Chicago, Illinois, United States
  • Harumitsu Hirata
    Ophthalmology, Weill Cornell Medical College, New York City, New York, United States
  • Footnotes
    Commercial Relationships   Evguenia Ivakhnitskaia, None; Kamila Mizerska, None; Valentina Dallacasagrande, None; Victor Guaiquil, None; Mark Rosenblatt, None; Harumitsu Hirata, None
  • Footnotes
    Support  NIH Grants EY023555 (HH); EY018594 (MIR); the Research to Prevent Blindness Grants to the Department of Ophthalmology and Visual Sciences, University of Illinois-Chicago; the Research to Prevent Blindness Grants to Department of Ophthalmology, Weill Cornell Medical College
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 3284. doi:https://doi.org/
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      Evguenia Ivakhnitskaia, Kamila Mizerska, Valentina Dallacasagrande, Victor H Guaiquil, Mark Rosenblatt, Harumitsu Hirata; Thirty-minute ocular application of benzalkonium chloride (BAK) leads to a disappearance of neuronal spikes associated with a marked fragmentation of tight junctions and corneal nerves in rodents: implications for dry eye disease.. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3284. doi: https://doi.org/.

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

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Abstract

Purpose : Many risk factors contribute to dry eye disease, which is characterized by abnormal corneal morphology. Drug toxicity constitutes a major risk factor for dry eye disease. The chronic use of the preservative, BAK, contained in phenylephrine chloride (ophthalmic solution used during routine eye examination), has been shown to cause death of corneal epithelial cells and to alter corneal nerve morphology. However, its acute effects on tight junctions and corneal nerve functions have not been investigated. Here we examined the electrophysiological and immunohistochemical consequences of a brief ocular instillation of BAK in rodents.

Methods : In isoflurane-anesthetized rats, we performed in vivo extracellular recordings from single trigeminal ganglion neurons innervating the cornea before and after ocular instillation of 2.5% phenylephrine HCl (PHE) with or without 0.01% BAK or 0.01% BAK only solution. After the electrophysiology experiments, the same corneas were immunohistochemically processed to label the intraepithelial corneal nerves (class III β-tubulin) and tight junctions (ZO-1).

Results : Within 30 min after the application of BAK or PHE with BAK as preservative, a propagation of the action potentials of the corneal neurons suddenly failed (the signal disappeared) and did not return after washout. When subsequently the same corneas were examined immunohistochemically, the tight junctions and the nerve terminals showed severe damage with extensive fragmentation. The typical polygonal structure of a ZO1-stained tight junction seen in normal corneas was severely disintegrated, and the corneal nerve terminals showed early signs of acute axonal degeneration.

Conclusions : Our results revealed that short exposure to ophthalmic solutions with low BAK concentrations used in routine eye examinations has profound consequences on corneal nerve and epithelial integrity; hence, caution is warranted with such uses. The long-term consequences of this short exposure on corneal nerves and tight junctions is currently under investigation. Overall, these studies may lead to a better understanding of the pathogenesis of dry eye disease.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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