Human corneal cell culture models for drug toxicity studies

被引:53
作者
Ronkko, Seppo [1 ]
Vellonen, Kati-Sisko [1 ]
Jarvinen, Kristiina [1 ]
Toropainen, Elisa [1 ]
Urtti, Arto [1 ,2 ]
机构
[1] Univ Eastern Finland, Sch Pharm, Fac Hlth Sci, POB 1627, Kuopio 70211, Finland
[2] Univ Helsinki, Ctr Drug Res, Div Pharmaceut Biosci, Fac Pharm, POB 56, FIN-00014 Helsinki, Finland
基金
芬兰科学院;
关键词
Ocular toxicity; Corneal cell culture; ADME prediction; In vitro model; Ocular bioavailability; EPITHELIAL STEM-CELLS; VITRO TISSUE MODELS; EYE IRRITATION TEST; HCE TEST METHOD; IN-VITRO; ENDOTHELIAL-CELLS; PROTEIN EXPRESSION; AMNIOTIC MEMBRANE; OCULAR IRRITATION; ABC TRANSPORTERS;
D O I
10.1007/s13346-016-0330-y
中图分类号
TH7 [仪器、仪表];
学科分类号
0804 ; 080401 ; 081102 ;
摘要
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.
引用
收藏
页码:660 / 675
页数:16
相关论文
共 151 条
[71]   Niche regulation of corneal epithelial stem cells at the limbus [J].
Li, Wei ;
Hayashida, Yasutaka ;
Chen, Ying-Ting ;
Tseng, Scheffer C. G. .
CELL RESEARCH, 2007, 17 (01) :26-36
[72]   Elucidating mechanisms of drug-induced toxicity [J].
Liebler, DC ;
Guengerich, FP .
NATURE REVIEWS DRUG DISCOVERY, 2005, 4 (05) :410-420
[73]   Corneal epithelial wound healing [J].
Lu, L ;
Reinach, PS ;
Kao, WWY .
EXPERIMENTAL BIOLOGY AND MEDICINE, 2001, 226 (07) :653-664
[74]   Identification of Human Fibroblast Cell Lines as a Feeder Layer for Human Corneal Epithelial Regeneration [J].
Lu, Rong ;
Bian, Fang ;
Lin, Jing ;
Su, Zhitao ;
Qu, Yangluowa ;
Pflugfelder, Stephen C. ;
Li, De-Quan .
PLOS ONE, 2012, 7 (06)
[75]   OCCLUDING JUNCTION STRUCTURE-FUNCTION RELATIONSHIPS IN A CULTURED EPITHELIAL MONOLAYER [J].
MADARA, JL ;
DHARMSATHAPHORN, K .
JOURNAL OF CELL BIOLOGY, 1985, 101 (06) :2124-2133
[76]   Oligopotent stem cells are distributed throughout the mammalian ocular surface [J].
Majo, Francois ;
Rochat, Ariane ;
Nicolas, Michael ;
Abou Jaoude, Georges ;
Barrandon, Yann .
NATURE, 2008, 456 (7219) :250-U51
[77]   PHARMACOKINETICS OF TOPICALLY APPLIED PILOCARPINE IN TH ALBINO RABBIT EYE [J].
MAKOID, MC ;
ROBINSON, JR .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1979, 68 (04) :435-443
[78]  
Mamalis N, 2006, J CATARACT REFR SURG, V32, P324, DOI 10.1016/j.jcrs.2006.01.065
[79]  
Mamalis N., 2010, CATARACT SURG, P589
[80]   Extent of initial corneal injury as the mechanistic basis for ocular irritation: Key findings and recommendations for the development of alternative assays [J].
Maurer, JK ;
Parker, RD ;
Jester, JV .
REGULATORY TOXICOLOGY AND PHARMACOLOGY, 2002, 36 (01) :106-117