Expression of ABC-transporters in human corneal tissue and the transformed cell line, HCE-T.
J Ocul Pharmacol Ther
; 23(2): 172-81, 2007 Apr.
Article
em En
| MEDLINE
| ID: mdl-17444805
ABSTRACT
PURPOSE:
The aim of this study was to elucidate the expression pattern of transport proteins relevant to drug absorption in human cornea and to assess the human corneal epithelial cell line, HCE-T, regarding its use as an in vitro model for drug-absorption studies.METHODS:
Human corneal tissue and HCE-T cells were examined for the expression of P-glycoprotein (P-gp/MDR1), multidrug resistance-associated protein 1 (MRP1), multidrug resistance-associated protein 2 (MRP2), lung resistance-related protein (LRP), and breast cancer-resistance protein (BCRP), using reverse transcriptase-polymerase chain reaction and immunofluorescence microscopy. Moreover, transporter activity was measured by bi-directional flux studies across excised human cornea and HCE-T cell layers using a P-gp/MDR1 substrate, rhodamine 123 (Rh123).RESULTS:
Transport studies of Rh123 revealed no significant differences in fluxes in the apical-to-basolateral and basolateral-to-apical directions across excised human corneas or HCE-T cell layers, suggesting the absence or insignificant, if any, participation of P-gp/MDR1 to Rh123 fluxes. Of all the transporter proteins under investigation, only LRP was found in human cornea. By contrast, a signal for LRP was not found in HCE-T, but the expression of MRP1, MRP2, and BCRP could be confirmed. Of note is the lack of P-gp/MDR1 expression in any of the specimens we examined.CONCLUSIONS:
Only a limited array of ABC-transporters is functionally expressed in human cornea. The expression pattern of HCE-T cells appears to be widely different from that of the native corneal tissue. Hence, the in vitro model of human cornea, HCE-T, should be used with much caution when predicting transport rates across the human corneal epithelial barrier in vivo.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transportadores de Cassetes de Ligação de ATP
/
Epitélio Corneano
/
Córnea
/
Perfilação da Expressão Gênica
/
Modelos Biológicos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Ocul Pharmacol Ther
Assunto da revista:
FARMACOLOGIA
/
OFTALMOLOGIA
/
TERAPEUTICA
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Alemanha