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In vitro permeability
Cornea and blood-retinal barrier formed by the retinal pigment epithelium (RPE) pose a challenge for novel chemical entities and biomolecules to enter the eye. Assessing the ability of novel molecules to bypass these barriers should be conducted early in the drug development process.
Cornea:
Human corneal epithelial cells (HCE-T1, RIKEN, Japan) are important as preclinical tool in evaluating novel molecule’s ability to enter the eye by transcorneal route2-4.
Retinal pigment epithelium (RPE)
RPE is a tight cell monolayer between retina and choroidal blood vessels limiting the entry of molecules into retina following systemic administration. RPE cells derived from human induced pluripotent stem cells (PCi-RPE5, Phenocell, France) introduce the key phenotypic and functional characteristics of primary human RPE cells6.
Technical details
– Human induced pluripotent stem cell (iPSC)-derived retinal pigmented epithelial cells (PCi-RPE, Phenocell, France)
– Rhodamine B
– FITC-dextran 4 000 Da
– FITC-dextran 70 000 Da
Scientific excellence in every model
Corneal permeability
Cornea: key barrier in topical ocular drug delivery, HCE-T cells mimic cornea’s tight junctions and cellular structure
RPE permeability
iPSC-RPE: form tight junctions and polarized monolayers, effectively mimicking the outer blood-retinal barrier
Tight barriers
Tight barriers mimic physiological conditions. Accurate permeability measurements in HCE-T and iPSC-RPE models help distinguish between transcellular and paracellular transport which is essential for understanding how the drug moves through the barriers
References
- Araki-Sasaki K, Ohashi Y, Sasabe T, Hayashi K, Watanabe H, Tano Y, Handa H. An SV40-immortalized human corneal epithelial cell line and its characterization. IOVS 1995,36:614–621.
- Toropainen et al. Culture model of human corneal epithelium for prediction of ocular drug absorption. Invest Ophthalmol Vis Sci 2001,42(12):2942-2948.
- Reichl. Cell culture models of the human cornea – a comparative evaluation of their usefulness to determine ocular drug absorption in-vitro. J. Pharm. Pharmacol. 2008;60(3):299-307.
- Žiniauskaitė A, Cėpla V, Jelinskas T, Eimont R, Ulčinas A, Aldonytė R, Valiokas R, Kalesnykas G, Hakkarainen JJ. Introducing an Efficient In Vitro Cornea Mimetic Model for Testing Drug Permeability. Sci. 2021; 3(3):30.
- Maruotti J, Wahlin K, Gorrell D, Bhutto I, Lutty G, Zack DJ. A simple and scalable process for the differentiation of retinal pigment epithelium from human pluripotent stem cells. Stem Cells Transl Med. 2013,2(5):341-354.
- Hakkarainen JJ, Maruotti J, Seppänen A, Onteniente B, Kalesnykas G, Reinisalo M. hiPSC-derived RPE cells: Characterization of blood-retinal barrier properties and drug permeability. ARVO2016 Poster. Investigative Ophthalmology & Visual Science September
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