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Retinal Pigment Epithelial Cell Line with Fast Differentiation and Improved Barrier Properties

1
School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, 70210 Kuopio, Finland
2
Drug Research Programme, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, FI-00014 Helsinki, Finland
3
Laboratory of Biohybrid Technologies, Institute of Chemistry, St. Petersburg State University, Peterhof, 198504 St. Petersburg, Russia
4
Institute of Clinical Medicine, Department of Ophthalmology, Faculty of Health Sciences, University of Eastern Finland, 70210 Kuopio, Finland
*
Author to whom correspondence should be addressed.
Pharmaceutics 2019, 11(8), 412; https://doi.org/10.3390/pharmaceutics11080412
Received: 27 June 2019 / Revised: 26 July 2019 / Accepted: 2 August 2019 / Published: 13 August 2019
PDF [4199 KB, uploaded 13 August 2019]
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Abstract

Retinal pigment epithelium (RPE) acts as an outer blood–retinal barrier that limits the access of circulating xenobiotics to the eye. In addition, the RPE limits posterior elimination of intravitreally injected drugs to circulation. Thus, permeation in the RPE has a significant effect on ocular pharmacokinetics. The RPE is also a potentially important drug target in age-related macular degeneration. Therefore, the cell models of the RPE are important tools in ocular drug development, but poor availability and problems in reproducibility limit the use of primary RPE cell cultures. Furthermore, the best and widely used human cell line ARPE19 requires specialized culture conditions and a long time for cellular differentiation. In this paper, we describe a cell population arisen from the ARPE19 culture, with fast differentiation and improved barrier properties. This cell line, LEPI, forms clear microvilli and rapidly displays RPE-like cobblestone morphology after subculture in simple culture conditions. The LEPI cells show RPE-specific functions and expression of RPE65, ezrin, and BEST1 proteins. On filter, the LEPI cells develop tighter barrier than the ex vivo bovine RPE-choroid: permeability coefficients of beta-blockers (atenolol, nadolol, timolol, pindolol, metoprolol, betaxolol) ranged from 0.4 × 10−6 cm/sec to 2.3 × 10−6 cm/sec depending on the drug lipophilicity. This rapidly differentiating cell line will be an asset in ocular studies since it is easily maintained, it grows and differentiates quickly and does not require specialized culture conditions for differentiation. Thus, this cell line is suitable for both small scale assays and high throughput screening in drug discovery and development.
Keywords: retinal pigment epithelium; outer blood–retinal barrier; cell line; ARPE19; differentiation; tight junctions; microvilli; drug permeation; beta-blockers retinal pigment epithelium; outer blood–retinal barrier; cell line; ARPE19; differentiation; tight junctions; microvilli; drug permeation; beta-blockers
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Hellinen, L.; Pirskanen, L.; Tengvall-Unadike, U.; Urtti, A.; Reinisalo, M. Retinal Pigment Epithelial Cell Line with Fast Differentiation and Improved Barrier Properties. Pharmaceutics 2019, 11, 412.

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