Human organotypic corneal equivalents for in-vitro drug absorption and metabolism studies
Project code: BfR-ZEBET-08-1328-306
Contract period: 01.06.2009 - 31.12.2014
Purpose of research: Experimental development
The purpose of this project is further characterization of reconstructed organotypic human corneal equivalent as replacement for animal experiments in drug absorption and metabolism studies in terms of the expression of active transport proteins and metabolic enzymes in corneal tissue.
For the Hemicornea construct expression of efflux transporters MRP1, MRP4, MRP5 and BCRP as well as of metabolic enzymes GSTO1, GSTP1 and CYP2D6 was detected. Expression was determined at mRNA, protein as well as functionality level. However, differences were found between the different cornea models and species.
Publications: Kölln, C. and Reichl, S.; mRNA Expression of Metabolic Enzymes in Human Cornea, Corneal Cell Lines, and Hemicornea Constructs. Journal of Ocular Pharmacology and Therapeutics, Vol. 28, No. 3, 271-277 (2012). Verstraelen, J. and Reichl, S.; Expression analysis of MDR1, BCRP and MRP3 transporter proteins in different in vitro and ex vivo cornea models for drug absorption studies. International Journal of Pharmaceutics, 441, 765-775 (2013). Verstraelen, J. and Reichl, S.; Multidrug Resistance-Associated Protein (MRP1, 2, 4 and 5) Expression in Human Corneal Cell Culture Models and Animal Corneal Tissue. Mol. Pharmaceutics, 11, 2160-2171 (2014). Verstraelen, J. and Reichl, S.; Upregulation of P-glycoprotein expression by ophthalmic drugs in different corneal in-vitro models. Journal of Pharmacy and Pharmacology, 67, 605-615 (2015). Kölln, C. and Reichl, S.; Cytochrome P450 Activity in Ex Vivo Cornea Models and a Human Cornea construct. Journal of Pharmaceutical Sciences, 105, 2204-2212 (2016).