Paper
Alkylphosphocholines inhibit proliferation of human retinal pigment epithelial cells.
Published Aug 1, 2003 · K. Eibl, B. Banas, C. Schoenfeld
Investigative ophthalmology & visual science
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Abstract
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 (32)P-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. IC(50)s of all APCs varied between 8.5 micro M (erucyl-phosphocholine, C22:1-PC), 9.0 micro M (Z)-12-heneicosenyl-phosphocholine, C21:1-PC), 11.0 micro M (Z)-10-eicosenyl-phosphocholine, C20:1-PC), and 26.5 micro M (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.
Alkylphosphocholines (APCs) inhibit proliferation of retinal pigment epithelial cells and matrix contraction in vitro at nontoxic concentrations, making them promising candidates for treating RPE-mediated proliferative processes like proliferative vitreoretinopathy.
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