Localization of Multidrug Resistance-Associated Protein 2 in the Nonpigmented Ciliary Epithelium of the Eye

• DOI: 10.1124/jpet.108.149625
• Publication Date: 2009-02-07T09:02:34Z
• Authors: Ryan M. Pelis; Mohammad Shahidullah; Sikha Ghosh; Miguel Coca-Prados; Stephen H. Wright; Nicholas A. Delamere
• Keywords: Apical membrane

The nonpigmented epithelium (NPE) of the ciliary body represents an important component blood-aqueous barrier eye. Many therapeutic drugs penetrate poorly across NPE into aqueous humor eye interior. Several these drugs, such as methotrexate, vincristine, and etoposide, are substrates multidrug resistance-associated protein 2 (MRP2). Abundant MRP2 was detected by Western blot in homogenates human freshly dissected porcine NPE. In cultured NPE, intracellular accumulation calcein (1.8-fold), 5-(and-6)-carboxy-2',7'-dichlorofluorescein (22.1-fold), doxorubicin (1.9-fold) significantly increased presence 50 microM MK571 ((E)-3-[[[3-[2-(7-chloro-2-quinolinyl)-ethenyl]phenyl]-[[3-dimethylamino)-3-oxopropyl]thio]methyl]thio]-propanoic acid), MRP inhibitor. addition, substrate glutathione methylfluorescein (4.3-fold), 500 indomethacin (2.6-fold), cyclosporin A (2.1-fold) but not sulfinpyrazone. These data consistent with MRP2-mediated transport activity mRNA (reverse transcriptase-polymerase chain reaction) (Western blot) were cells. Immunolocalization studies native eyes showed at apical interface pigmented cell layers. Close examination immunoreactivity supported conclusion that is localized membrane cells may be involved protecting intraocular tissues from exposure to potentially harmful toxins.