School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, 70210 Kuopio, Finland.
Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, 70210 Kuopio, Finland.
Eur J Pharm Biopharm. 2023 Mar;184:181-188. doi: 10.1016/j.ejpb.2023.01.026. Epub 2023 Feb 4.
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 value range, with relatively high permeation rates (5.2-26 × 10 cm/s). In contrast, hESC-RPE cells efficiently restricted the drug flux, and displayed even lower P values than those reported for bovine RPE-choroid, with the range of 0.4-32 cm/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.
视网膜色素上皮 (RPE) 细胞单层形成了外血视网膜屏障，在眼部药代动力学中起着至关重要的作用。尽管已经有几种 RPE 细胞模型，但尚未对其药物通透性的屏障特性进行系统比较。我们通过研究 9 种药物（氨曲南、环丙沙星、地塞米松、氟康唑、更昔洛韦、酮咯酸、甲氨蝶呤、伏立康唑和奎尼丁）在细胞单层中的渗透性，比较了 RPE 次级细胞系 (ARPE19 和 ARPE19mel) 以及原代 (hfRPE) 和干细胞衍生的 RPE (hESC-RPE) 细胞的屏障特性。ARPE19、ARPE19mel 和 hfRPE 细胞的 P 值范围较窄，渗透性较高（5.2-26×10 cm/s）。相比之下，hESC-RPE 细胞有效地限制了药物通量，其 P 值比牛 RPE-脉络膜报道的值还要低，范围为 0.4-32 cm/s。因此，ARPE19、ARPE19mel 和 hfRPE 细胞未能形成紧密的屏障，而 hESC-RPE 细胞对药物通量的限制程度与牛 RPE-脉络膜相似。因此，hESC-RPE 细胞是眼部药物发现的有价值的工具。
