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Alkylphosphocholines Inhibit Proliferation of Human Retinal Pigment Epithelial Cells

¹From the Departments of Ophthalmology and ²Medicine, Ludwig-Maximilians-University, Munich, Germany; and the ³Department of Anatomy, Friedrich Alexander University, Erlangen, Germany.

PURPOSE. To investigate the effect and mechanism of action of alkylphosphocholines (APCs) on proliferation of human retinal pigment epithelium (RPE) cells and RPE-mediated collagen matrix contraction in vitro.

METHODS. Cultured RPE cells of five human donors were treated with four APCs in the presence of fetal calf serum. Proliferation was assessed by the tetrazolium dye-reduction (MTT) assay and by counting the number of cells dividing in culture. The effect of APCs on RPE-mediated matrix contraction was determined in three-dimensional collagen gels. Cell viability was tested by the trypan blue exclusion assay. As a possible mechanism of APC action, protein kinase C (PKC) activity was quantified by scintillation counting of ³²P-labeled phosphate transferred to a PKC-specific substrate.

RESULTS. All APCs inhibited RPE proliferation and RPE–mediated collagen matrix contraction in a dose-dependent manner in vitro. The antiproliferative and anticontractile effect of APCs increased with elongation of the fatty acid chain beyond C20. IC₅₀s of all APCs varied between 8.5 µM (erucyl-phosphocholine, C22:1-PC), 9.0 µM (Z)-12-heneicosenyl-phosphocholine, C21:1-PC), 11.0 µM (Z)-10-eicosenyl-phosphocholine, C20:1-PC), and 26.5 µM (oleyl-phosphocholine, C18:1-PC). Trypan blue staining revealed a toxicity below 5% for all APCs within the concentration interval tested. PKC activity was significantly reduced by all four APCs, with C22:1-PC being the most effective.

CONCLUSIONS. APCs inhibit proliferation of RPE cells and RPE-mediated matrix contraction in vitro at nontoxic concentrations. This effect seems to be exerted through inhibition of PKC activity. Therefore, APCs are promising candidates for treatment of RPE-mediated proliferative processes such as proliferative vitreoretinopathy.

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				K. H. Eibl, G. P. Lewis, K. Betts, K. A. Linberg, A. Gandorfer, A. Kampik, and S. K. Fisher The Effect of Alkylphosphocholines on Intraretinal Proliferation Initiated by Experimental Retinal Detachment Invest. Ophthalmol. Vis. Sci., March 1, 2007; 48(3): 1305 - 1311. [Abstract] [Full Text] [PDF]

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