The isoflavonoid genistein is known as a potent inhibitor of proliferation in endothelial cells and in some tumor cell lines in vitro and in vivo. Cell growth arrest is mediated by inhbitor of the tyrosine-kinase receptor, a target for many growth factors such as fibroblast growth factor, platelet-derived growth factor, epidermal growth-factor and vascular endothelial growth factor, which may play a role in the development of proliferative vitreoretinopathy (PVR). In this study we report on the antiproliferative effect of genistein on retinal pigment epithelial cells (RPE), which is the major cell type involved in PVR.
Methods: Cell culture experiments using porcine RPE treated with different concentrations (5 up to 100 microgram/ml) of genistein in minimum essential medium +10% fetal calf serum. Inhibition of proliferation was demonstrated by two different methods: (1) uptake of 5-bromo-2-deoxyuridin (BrdU) in S phase after different exposure times (2) expression of proliferating cell nuclear antigen 72 h after scratching confluent RPE.
Results: Exposure of RPE to genistein resulted in a concentration-dependent inhibition of cell proliferation at concentrations over 25 microgram/ml geinistein. BrdU incorporation was reduced to 65% after 24- and 48-hour treatment with 100 microgram/ml genistein in comparison with the untreated cells. Proliferation of RPE growing into the artificial wound was inhibited when cells were exposed for 72 h to more than 25 microgram/ml genistein.
Conclusions: Genistein at concentrations over 25 microgram/ml inhibits RPE proliferation. Further studies will be required to determine the applicability of genistein or other phytoestrogens in order to prevent uncontrolled wound healing processes such as PVR.
Copyright 2000 S. Karger AG, Basel.