Human corneal cell culture models for drug toxicity studies

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• 作者：Seppo Rönkkö ; Kati-Sisko Vellonen…
• 关键词：Ocular toxicity ; Corneal cell culture ; ADME prediction ; In vitro model ; Ocular bioavailability
• 刊名：Drug Delivery and Translational Research
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：6
• 期：6
• 页码：660-675
• 全文大小：1,084 KB
• 刊物主题：Pharmaceutical Sciences/Technology;
• 出版者：Springer US
• ISSN：2190-3948
• 卷排序：6

文摘

In vivo toxicity and absorption studies of topical ocular drugs are problematic, because these studies involve invasive tissue sampling and toxic effects in animal models. Therefore, different human corneal models ranging from simple monolayer cultures to three-dimensional models have been developed for toxicological prediction with in vitro models. Each system has its own set of advantages and disadvantages. Use of non-corneal cells, inadequate characterization of gene-expression profiles, and accumulation of genomic aberrations in human corneal models are typical drawbacks that decrease their reliability and predictive power. In the future, further improvements are needed for verifying comparable expression profiles and cellular properties of human corneal models with their in vivo counterparts. A rapidly expanding stem cell technology combined with tissue engineering may give future opportunities to develop new tools in drug toxicity studies. One approach may be the production of artificial miniature corneas. In addition, there is also a need to use large-scale profiling approaches such as genomics, transcriptomics, proteomics, and metabolomics for understanding of the ocular toxicity.