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Human & Experimental Toxicology
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research-article

Evaluation of the selected barrier properties of retinal pigment epithelial cell line ARPE-19 for an in-vitro blood-brain barrier model

H Nevala

Medical School, Cell Research Center, University of Tampere, Finland heidi.nevala{at}uta.fi

T Ylikomi

Medical School, Cell Research Center, University of Tampere, Finland; Tampere University Hospital, Tampere, Finland

H Tähti

Medical School, Cell Research Center, University of Tampere, Finland

In-vitro models that maintain complex transport mechanisms and structural properties associated with the blood-brain barrier in vivo would be useful in drug permeability and neurotoxicological studies. To evaluate the suitability of a human retinal pigment epithelial cell line for a blood-brain barrier model, we have compared the barrier properties of the human retinal pigment epithelial cell line ARPE-19, the human colonic adenocarcinoma cell line Caco-2, and primary porcine microvessel endothelial cells. The tight junction proteins occludin and ZO-1 were stained immunocytochemically. The paracellular ionic permeability was evaluated by measuring the trans-epithelial or trans-endothelial electric resistance. To evaluate the active transport mechanisms, the existence and the activity of the efflux transporters, P-glycoprotein and multidrug resistance-associated proteins, were studied. All the cell types in this study stained positively for occludin and ZO-1. However, the trans-endothelial electric resistance of ARPE-19 cells was low compared with that of primary porcine microvessel endothelial cell and Caco-2 cells. In addition, both the P-glycoprotein expression and its activity in ARPE-19 cells were low. In conclusion, the barrier properties of the human ARPE-19 cell line were not satisfactory for a blood-brain barrier model. For future studies, it is important to develop a human brain endothelial cell line with expression of the complex in-vivo properties of the blood-brain barrier.

Key Words: ARPE-19 • blood-brain barrier • Caco-2 • MRP1 • occludin • P-glycoprotein • primary porcine microvessel endothelial cell • retinal barrier • ZO-1

Human & Experimental Toxicology, Vol. 27, No. 10, 741-749 (2008)
DOI: 10.1177/0960327107082230
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