{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,18]],"date-time":"2025-05-18T04:07:33Z","timestamp":1747541253655,"version":"3.40.5"},"reference-count":59,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2015,5,1]],"date-time":"2015-05-01T00:00:00Z","timestamp":1430438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"German Federal Institute for Risk Assessment","award":["FK 3\u20131328-306\u201352054369"],"award-info":[{"award-number":["FK 3\u20131328-306\u201352054369"]}]},{"name":"German Academic Exchange Service"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>The purpose of this study was to analyse P-glycoprotein (P-gp) expression in different human in-vitro cornea models (HCE-T epithelial model and Hemicornea construct) after stimulation with P-gp substrates (rhodamine 123, levofloxacin and acebutolol).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The influence of P-gp substrates on mRNA expression was analysed using reverse transcriptase polymerase chain reaction (PCR) and real-time PCR. The effect of stimulation on the transporter functionality was estimated with a digoxin efflux assay. The Caco-2 cell line was used as positive control.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key findings<\/jats:title><jats:p>The reverse transcriptase PCR results showed an increase in band intensity compared with the control medium for all substrates. The real-time PCR for the Caco-2 and HCE-T epithelial model yielded a similar outcome, in which all tested substrates upregulated P-gp. In contrast, the Hemicornea construct showed no significant increase in the mRNA expression after stimulation. Both in-vitro models possessed similar drug transport profiles after stimulation. A significantly increased efflux of digoxin was measured after 24 and 72 h of stimulation with levofloxacin and acebutolol.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The expression and functionality of the P-gp in corneal tissue can be influenced through time exposure with specific substrates. However, the exact mechanism still requires further elucidation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jphp.12357","type":"journal-article","created":{"date-parts":[[2015,1,23]],"date-time":"2015-01-23T13:05:38Z","timestamp":1422018338000},"page":"605-615","source":"Crossref","is-referenced-by-count":4,"title":["Upregulation of P-glycoprotein expression by ophthalmic drugs in different corneal in-vitro models"],"prefix":"10.1093","volume":"67","author":[{"given":"Jessica","family":"Verstraelen","sequence":"first","affiliation":[{"name":"Institut f\u00fcr Pharmazeutische Technologie, Technische Universit\u00e4t Braunschweig , Braunschweig,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan","family":"Reichl","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Pharmazeutische Technologie, Technische Universit\u00e4t Braunschweig , Braunschweig,","place":["Germany"]},{"name":"Zentrum f\u00fcr Pharmaverfahrenstechnik, Technische 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