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.
Nakamura
Tadahiro
T
Department of Hospital Pharmacy, Nagasaki University Hospital of Medicine and Dentistry, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
Yamada
Mikiko
M
Teshima
Mugen
M
Nakashima
Mikiro
M
To
Hideto
H
Ichikawa
Nobuhiro
N
Sasaki
Hitoshi
H
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