RRC ID 61610
著者 Yamaguchi H, Takezawa T.
タイトル Fabrication of a Corneal Model Composed of Corneal Epithelial and Endothelial Cells via a Collagen Vitrigel Membrane Functioned as an Acellular Stroma and Its Application to the Corneal Permeability Test of Chemicals.
ジャーナル Drug Metab Dispos
Abstract A collagen vitrigel membrane (CVM) we developed can function as both a scaffold for cells and a pathway for chemicals. To extrapolate the corneal permeability of chemicals in vivo, we proposed six corneal models using the CVM. Thin and thick CVMs were used as models for Bowman's membrane (BM) and an acellular stroma (AS), respectively. Models for a corneal epithelium (CEpi), a CEpi-AS, a CEpi-endothelium (Endo), and a CEpi-AS-Endo were fabricated by culturing corneal epithelial cells and/or corneal endothelial cells on the surface of CVMs. Subsequently, the permeability coefficient (Papp) value of each model was calculated using five chemicals with different molecular radii; cyanocobalamin and four fluorescein isothiocyanate-dextrans (FD) (FD-4, FD-10, FD-20, and FD-40). The slopes of Papp versus molecular radii of those chemicals in the both BM and AS models were almost similar to data using an excised rabbit corneal stroma. The ratios of Papp values in models for BM, CEpi, and CEpi-Endo against those in data using an excised rabbit cornea were calculated as 75.4-fold, 6.4-fold, and 4.5-fold for FD-4, and 38.7-fold, 10.0-fold, and 4.2-fold for FD-10, respectively. Similarly, those in models for AS, CEpi-AS, and CEpi-AS-Endo were calculated as 26.1-fold, 2.5-fold, and 0.6-fold for FD-4, and 26.1-fold, 1.5-fold, and 0.6-fold for FD-10, respectively. These results suggest that the CEpi-AS-Endo model with both the barrier function of corneal cell layers and the diffusion capacity of chemicals in thick CVM is most appropriate for extrapolating the corneal permeability of chemicals in vivo.
巻・号 46(11)
ページ 1684-1691
公開日 2018-11-1
DOI 10.1124/dmd.118.080820
PII dmd.118.080820
PMID 29844140
MeSH Animals Cell Line Collagen / metabolism* Cornea / metabolism* Corneal Stroma / metabolism* Dextrans / metabolism Endothelial Cells / metabolism* Epithelium, Corneal / metabolism* Fluorescein-5-isothiocyanate / analogs & derivatives Fluorescein-5-isothiocyanate / metabolism Humans Permeability Rabbits
IF 3.231
リソース情報
ヒト・動物細胞 HCE-T(RCB2280)