Electrophysiological characterization of tight junctional pathway of rabbit cornea treated with ophthalmic ingredients.
The purpose of this study was to investigate the continuous and real-time influence of ophthalmic ingredients on rabbit cornea by monitoring electrophysiological characteristics. The tight junctional permeabilities of FITC-dextran 4,400 (FD-4) was also determined through the cornea in the presence of ophthalmic ingredients. Intact cornea showed approximately one k-ohmxcm(2) of transepithelial electrical resistance (TEER) and extremely low permeability of FD-4. The ophthalmic ingredients used in the present study were benzalkonium chloride (BK; 0.002%, 0.01%, 0.05%), ethylenediaminetetraacetic acid (EDTA; 0.5%), capric acid (C10; 0.25%), saponin (SP; 0.1%), taurocholic acid (TA; 1.0%) and sodium dodecyl sulfate (SDS; 0.01%). They were previously reported to be effective on corneal penetrations of various drugs at those concentrations without severe toxicity. These ingredients decreased TEER and increased corneal permeability of FD-4. BK reduced TEER in a concentration-dependent manner. There was a significant correlation (gamma=0.860) between the permeability coefficient (Papp) of FD-4 and conductance (Gm), which is the reciprocal value of TEER. It was also indicated that Papp and Gm have a relationship with the corneal cytotoxicity of the ingredients. In conclusion, an electrophysiological method using isolated cornea was very useful to determine the continuous and real-time influence of ophthalmic ingredients on the cornea. In this method, electrophysiological conductance must be able to predict corneal tight junction permeability and the corneal cytotoxicity of ingredients.
Department of Hospital Pharmacy, Nagasaki University Hospital of Medicine and Dentistry, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
Tadahiro
T
Nakamura
Mikiko
M
Yamada
Mugen
M
Teshima
Mikiro
M
Nakashima
Hideto
H
To
Nobuhiro
N
Ichikawa
Hitoshi
H
Sasaki
D000042:Absorption; D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003315:Cornea / Q000166:cytology* / Q000187:drug effects; D003627:Data Interpretation, Statistical; D003911:Dextrans; D015194:Diffusion Chambers, Culture; D004594:Electrophysiology; D016650:Fluorescein-5-isothiocyanate; D066298:In Vitro Techniques; D008297:Male; D009883:Ophthalmic Solutions / Q000494:pharmacology*; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects*; D019108:Tight Junctions / Q000187:drug effects*
D003911:Dextrans; D009883:Ophthalmic Solutions; D016650:Fluorescein-5-isothiocyanate