title: Sensitive and real-time method for evaluating corneal barrier considering tear flow.
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.
authors.affiliation: Department of Hospital Pharmacy, Nagasaki University Hospital, Nagasaki 852-8501, Japan.
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Nakamura
authors.forename: Mugen
authors.initials: M
authors.lastname: Teshima
authors.forename: Takashi
authors.initials: T
authors.lastname: Kitahara
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sasaki
authors.forename: Masafumi
authors.initials: M
authors.lastname: Uematsu
authors.forename: Takashi
authors.initials: T
authors.lastname: Kitaoka
authors.forename: Mikiro
authors.initials: M
authors.lastname: Nakashima
authors.forename: Koyo
authors.initials: K
authors.lastname: Nishida
authors.forename: Junzo
authors.initials: J
authors.lastname: Nakamura
authors.forename: Shun
authors.initials: S
authors.lastname: Higuchi
mesh_terms: D000818:Animals; D001548:Benzalkonium Compounds / Q000009:adverse effects*; D003316:Corneal Diseases / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D017097:Electric Impedance; D004594:Electrophysiology / Q000295:instrumentation / Q000379:methods*; D019573:Epithelium, Corneal / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D023421:Models, Animal; D009883:Ophthalmic Solutions / Q000009:adverse effects*; D011310:Preservatives, Pharmaceutical / Q000009:adverse effects*; D011817:Rabbits; D013666:Tears; D019108:Tight Junctions / Q000187:drug effects / Q000473:pathology
chemical_list: D001548:Benzalkonium Compounds; D009883:Ophthalmic Solutions; D011310:Preservatives, Pharmaceutical