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QobuR-用于临床前药物筛选的新型体外人角膜上皮模型。

QobuR - A new in vitro human corneal epithelial model for preclinical drug screening.

机构信息

Instituto Universitario Fernández-Vega, Fundación de Investigación Oftalmológica, Universidad de Oviedo, Oviedo, Spain.

Instituto Universitario Fernández-Vega, Fundación de Investigación Oftalmológica, Universidad de Oviedo, Oviedo, Spain.

出版信息

Eur J Pharm Biopharm. 2019 Mar;136:164-173. doi: 10.1016/j.ejpb.2019.01.023. Epub 2019 Jan 25.

DOI:10.1016/j.ejpb.2019.01.023
PMID:30690064
Abstract

A new in vitro human corneal epithelial model (QobuR) obtained from normal limbal tissue has been developed to study ocular irritancy of different ophthalmic compounded drugs. Phenotypical characterization and trans-epithelial electrical resistance (TEER) of QobuR revealed essential similarities compared with a native human cornea, displaying functional markers and TEER values near 1500 Ωcm at day 7th of cellular differentiation. Using this model, ocular irritancy and barrier integrity alterations were evaluated using MTT reaction and variations in TEER. We found that some of the Non-Irritant products evaluated still damage the corneal epithelial integrity and current protocols for ocular irritancy should therefore include a barrier integrity evaluation. Moreover, in order to comprehensively evaluate corneal permeability of the active ingredients, we propose the use of QobuR as an all-in-one alternative method for evaluating ocular irritancy, barrier disruptions and permeability rates of topically applied ocular drugs to improve current in vitro drug testing procedures.

摘要

已开发出一种新的体外人角膜上皮模型 (QobuR),源自正常的角膜缘组织,用于研究不同眼科复方药物的眼部刺激性。与天然人角膜相比,QobuR 的表型特征和跨上皮电阻 (TEER) 显示出重要的相似性,在细胞分化的第 7 天显示出功能性标记物和接近 1500 Ωcm 的 TEER 值。使用该模型,通过 MTT 反应和 TEER 的变化评估眼部刺激性和屏障完整性改变。我们发现,评估的一些非刺激性产品仍会损害角膜上皮完整性,因此,眼部刺激性的当前方案应包括对屏障完整性的评估。此外,为了全面评估活性成分的角膜通透性,我们建议使用 QobuR 作为一种综合替代方法来评估眼部刺激性、屏障破坏和局部应用眼部药物的通透性,以改进当前的体外药物测试程序。

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