Sensitive and Real-Time Method for Evaluating Corneal Barrier Considering Tear Flow

Tadahiro Nakamura; Mugen Teshima; Takashi Kitahara; Hitoshi Sasaki; Masafumi Uematsu; Takashi Kitaoka; Mikiro Nakashima; Koyo Nishida; Junzo Nakamura; Shun Higuchi

doi:10.1248/bpb.33.107

Regular Articles

Sensitive and Real-Time Method for Evaluating Corneal Barrier Considering Tear Flow

Tadahiro Nakamura, Mugen Teshima, Takashi Kitahara, Hitoshi Sasaki, Masafumi Uematsu, Takashi Kitaoka, Mikiro Nakashima, Koyo Nishida, Junzo Nakamura, Shun Higuchi

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Tadahiro Nakamura
Department of Hospital Pharmacy, Nagasaki University Hospital
Mugen Teshima
Department of Hospital Pharmacy, Nagasaki University Hospital
Takashi Kitahara
Department of Hospital Pharmacy, Nagasaki University Hospital
Hitoshi Sasaki
Department of Hospital Pharmacy, Nagasaki University Hospital
Masafumi Uematsu
Department of Ophthalmology and Visual Sciences, Graduate School of Biomedical Sciences, Nagasaki University
Takashi Kitaoka
Department of Ophthalmology and Visual Sciences, Graduate School of Biomedical Sciences, Nagasaki University
Mikiro Nakashima
Department of Clinical Pharmacy, Graduate School of Biomedical Sciences, Nagasaki University
Koyo Nishida
Department of Clinical Pharmacy, Graduate School of Biomedical Sciences, Nagasaki University
Junzo Nakamura
Department of Clinical Pharmacy, Graduate School of Biomedical Sciences, Nagasaki University
Shun Higuchi
Department of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Kyushu University

Keywords: electrophysiological method, mimicking tear flow, corneal barrier, corneal transepithelial electrical resistance, Ussing chamber, benzalkonium chloride

JOURNAL FREE ACCESS

2010 Volume 33 Issue 1 Pages 107-110

DOI https://doi.org/10.1248/bpb.33.107

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Abstract

We developed a new electrophysiological method mimicking tear flow to evaluate the epithelial tight junction of rabbit cornea quantitatively. We investigated the effect of tear flow on the corneal damage induced by ophthalmic preservatives using this method. An Ussing chamber system with Ag/AgCl electrodes was used in the electrophysiological experiment. The excised rabbit cornea was mounted in the Ussing chamber and the precorneal solution in the chamber was perfused with a peristaltic pump at the rate of human tear flow. Corneal transepithelial electrical resistance (TEER) was monitored as corneal barrier ability. In the electrophysiological method mimicking tear flow, we observed stable TEER, which rapidly decreased with benzalkonium chloride (BAC), an eye drop preservative. Using this system, we first found that 0.004% BAC decreased corneal TEER reversibly. A high concentration of BAC showed strong irreversible damage to the tight junction. The influence of BAC on corneal TEER was not only concentration-dependent but also tear flow rate-dependent. The electrophysiological method mimicking tear flow was useful to evaluate the corneal barrier quantitatively. Using this method, we clarified that the tear flow was important to protect the corneal damage induced by preservatives.

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