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

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http://hdl.handle.net/10138/305637

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Hellinen , L , Pirskanen , L , Tengvall-Unadike , U , Urtti , A & Reinisalo , M 2019 , ' Retinal Pigment Epithelial Cell Line with Fast Differentiation and Improved Barrier Properties ' , Pharmaceutics , vol. 11 , no. 8 , 412 . https://doi.org/10.3390/pharmaceutics11080412

Title: Retinal Pigment Epithelial Cell Line with Fast Differentiation and Improved Barrier Properties
Author: Hellinen, Laura; Pirskanen, Lea; Tengvall-Unadike, Unni; Urtti, Arto; Reinisalo, Mika
Contributor: University of Helsinki, Drug Research Program
Date: 2019-08
Language: eng
Number of pages: 12
Belongs to series: Pharmaceutics
ISSN: 1999-4923
URI: http://hdl.handle.net/10138/305637
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 x 10(-6 )cm/sec to 2.3 x 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.
Subject: retinal pigment epithelium
outer blood-retinal barrier
cell line
ARPE19
differentiation
tight junctions
microvilli
drug permeation
beta-blockers
ARPE-19 CELLS
EXPRESSION
PERMEABILITY
317 Pharmacy
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