Human corneal cell culture models for drug toxicity studies.
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.
School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O.Box 1627, 70211, Kuopio, Finland.
Seppo
S
Rönkkö
School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O.Box 1627, 70211, Kuopio, Finland.
Kati-Sisko
KS
Vellonen
School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O.Box 1627, 70211, Kuopio, Finland.
Kristiina
K
Järvinen
School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O.Box 1627, 70211, Kuopio, Finland.
Elisa
E
Toropainen
School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O.Box 1627, 70211, Kuopio, Finland. arto.urtti@uef.fi.|Centre for Drug Research, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, 00014, Helsinki, Finland. arto.urtti@uef.fi.
Arto
A
Urtti
D018929:Cell Culture Techniques; D003315:Cornea / Q000187:drug effects*; D064420:Drug-Related Side Effects and Adverse Reactions; D004847:Epithelial Cells / Q000187:drug effects; D006801:Humans; D018675:Toxicity Tests / Q000379:methods*
ADME prediction; Corneal cell culture; In vitro model; Ocular bioavailability; Ocular toxicity