Ca2+ channels in retinal pigment epithelial cells regulate vascular endothelial growth factor secretion rates in health and disease.
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Ca2+ channels in retinal pigment epithelial cells regulate vascular endothelial growth factor secretion rates in health and disease. / Rosenthal, Rita; Heimann, Heinrich; Agostini, Hansjürgen; Martin, Gottfried; Hansen, Lutz Lothar; Strauss, Olaf.
in: MOL VIS, Jahrgang 13, 2007, S. 443-456.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Ca2+ channels in retinal pigment epithelial cells regulate vascular endothelial growth factor secretion rates in health and disease.
AU - Rosenthal, Rita
AU - Heimann, Heinrich
AU - Agostini, Hansjürgen
AU - Martin, Gottfried
AU - Hansen, Lutz Lothar
AU - Strauss, Olaf
PY - 2007
Y1 - 2007
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 13
SP - 443
EP - 456
JO - MOL VIS
JF - MOL VIS
SN - 1090-0535
ER -