Comparison of barrier properties of outer blood-retinal barrier models: Human stem cell-based models as a novel tool for ocular drug discovery

Abstract

<p>The retinal pigment epithelial (RPE) cell monolayer forms the outer blood–retinal barrier and has a crucial role in ocular pharmacokinetics. Although several RPE cell models are available, there have been no systematic comparisons of their barrier properties with respect to drug permeability. We compared the barrier properties of RPE secondary cell lines (ARPE19, and ARPE19mel) and both primary (hfRPE) and stem-cell derived RPE (hESC-RPE) cells by investigating the permeability of nine drugs (aztreonam, ciprofloxacin, dexamethasone, fluconazole, ganciclovir, ketorolac, methotrexate, voriconazole, and quinidine) across cell monolayers. ARPE19, ARPE19mel, and hfRPE cells displayed a narrow P<sub>app</sub> value range, with relatively high permeation rates (5.2–26 × 10<sup>−6</sup> cm/s). In contrast, hESC-RPE cells efficiently restricted the drug flux, and displayed even lower P<sub>app</sub> values than those reported for bovine RPE-choroid, with the range of 0.4–32 cm<sup>−6</sup>/s. Therefore, ARPE19, ARPE19mel, and hfRPE cells failed to form a tight barrier, whereas hESC-RPE cells restricted the drug flux to a similar extent as bovine RPE-choroid. Therefore, hESC-RPE cells are valuable tools in ocular drug discovery.</p>