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Sensitive and real-time method for evaluating corneal barrier considering tear flow.

Tadahiro Nakamura1, Mugen Teshima, Takashi Kitahara

  • 1Department of Hospital Pharmacy, Nagasaki University Hospital, Nagasaki 852-8501, Japan.

Biological & Pharmaceutical Bulletin
|January 5, 2010
PubMed
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A new electrophysiological method simulating tear flow quantifies corneal barrier function. This research reveals tear flow is crucial for protecting the cornea from preservative-induced damage, especially from benzalkonium chloride (BAC).

Area of Science:

  • Ophthalmology
  • Physiology
  • Biomedical Engineering

Background:

  • Ophthalmic preservatives can damage the corneal epithelium.
  • The protective role of natural tear flow against such damage is not fully understood.
  • Quantitative methods are needed to assess corneal barrier integrity under simulated physiological conditions.

Purpose of the Study:

  • To develop and validate a novel electrophysiological method that mimics natural tear flow.
  • To quantitatively evaluate the effect of tear flow on corneal epithelial tight junctions.
  • To investigate the protective role of tear flow against corneal damage induced by ophthalmic preservatives, specifically benzalkonium chloride (BAC).

Main Methods:

  • Development of an Ussing chamber system with Ag/AgCl electrodes for electrophysiological measurements.

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  • Perfusion of excised rabbit corneas with artificial tear solution at a rate mimicking human tear flow.
  • Monitoring of corneal transepithelial electrical resistance (TEER) as a measure of corneal barrier function.
  • Exposure of the cornea to varying concentrations of benzalkonium chloride (BAC) with and without simulated tear flow.

    • Main Results:

    • The developed method successfully maintained stable corneal transepithelial electrical resistance (TEER) under simulated tear flow.
    • Benzalkonium chloride (BAC) significantly decreased TEER, indicating damage to the corneal epithelial barrier.
    • The degree of BAC-induced damage was both concentration-dependent and tear flow rate-dependent.
    • Lower concentrations of BAC (0.004%) caused reversible damage, while higher concentrations led to irreversible tight junction disruption.

    Conclusions:

    • The novel electrophysiological method is effective for quantitatively evaluating corneal barrier function under simulated tear flow.
    • Tear flow plays a significant protective role in mitigating corneal damage caused by ophthalmic preservatives like BAC.
    • Understanding the interplay between tear flow and preservative toxicity is crucial for developing safer ophthalmic formulations.