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U. Becker, C. Ehrhardt, U.F. Schaefer, K.W. Ruprecht, C.M. Lehr; Multi–Drug Resistance Proteins Are Expressed in Human Cornea . Invest. Ophthalmol. Vis. Sci. 2005;46(13):2600.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:To study the expression of proteins with relevance to drug absorption such as P–glycoprotein (MDR1), multi drug resistance protein 1 (MRP1), multi drug resistance protein 2 (MRP2), lung resistance–related protein (LRP) and breast cancer resistance protein (BCRP) in human corneal epithelium. Introduction: The eye is considered a good target for local therapy, but absorption of certain drugs can be amended by multi–drug resistance (MDR). MDR has evolved as a problem in tumor therapy and intestinal drug delivery. Recently, the presence of MRP1 in rabbit corneal epithelial cell culture has been reported (Dey et al.), but few data is available on MDR expression and function in human corneal tissue. In this study, we determined the presence of MDR–related proteins in native human corneal epithelium. Methods: RT–PCR and western blotting of lysate gained from human corneas were performed. In addition, functionality of MDR1 was assessed by bi–directional transport studies across excised human cornea using a substrate, rhodamine 123 (Rh123), with and without presence of an MDR1–inhibitor, verapamil. Fluorescein–sodium (FLU) permeability was studied as a passively diffusing marker. Results: By RT–PCR the presence of the MDR–related proteins was assessed on the genomic level. Western blot studies gave similar information on the protein level. Rh123 showed a significant net secretion in transport studies (i.e., basolateral to apical transport) across intact cornea, which was regulated by verapamil. There was no significant directionality in FLU–transport, exhibiting permeability values in the range found in commonly used cell culture models. Conclusions: The presence of MDR–proteins in intact human cornea could be verified, giving new criteria for the evaluation of cell culture models representing the corneal epithelium. Acknowledgements: Ms. Gross and Dr. Eschmann (Ursapharm) are thanked for their support of this work. Drs. Baldes and Daum are thanked for their help in molecular biology, the staff of the Lions Corneabank, Homburg for their co–operation.
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