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  • Title: Ca2+ channels in retinal pigment epithelial cells regulate vascular endothelial growth factor secretion rates in health and disease.
    Author: Rosenthal R, Heimann H, Agostini H, Martin G, Hansen LL, Strauss O.
    Journal: Mol Vis; 2007 Mar 27; 13():443-56. PubMed ID: 17417605.
    Abstract:
    PURPOSE: Choroidal neovascularization (CNV) is the most severe complication in age-related macular degeneration. The major angiogenic factor involved is vascular endothelial growth factor (VEGF) secreted by the retinal pigment epithelium (RPE). Since RPE cells express neuroendocrine L-type Ca2+ channels we investigated their involvement in VEGF secretion in normal RPE cells and RPE cells from patients with CNV. METHODS: Freshly isolated and cultured RPE cells were studied using the patch-clamp technique and ELISA-based secretion assays. RESULTS: Both freshly isolated and cultured cells showed whole-cell Ba2+ currents with properties of L-type Ca2+ currents: high activation threshold, sensitivity to dihydropyridines (10 muM nifedipine) and slow inactivation. VEGF-A secretion was elevated by BayK8644 (10 microM) or basic fibroblast growth factor (bFGF, 10 ng/ml), both of which are able to activate L-type channels. Cells from CNV tissue also showed nifedipine-sensitive Ba2+ currents, which displayed a voltage-dependent activation at more negative potentials, faster inactivation and changed regulation by tyrosine kinase pp60(c-src). The CNV RPE cells showed higher VEGF secretion rates which were reduced by nifedipine. CONCLUSIONS: Thus, L-type Ca2+ channels in normal RPE cells regulate the secretion of VEGF. RPE cells from eyes with CNV maintain a VEGF secretion regulated by nifedipine-sensitve Ca2+ channels which might be of importance for the development of CNV.
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