Ca2+ channels in retinal pigment epithelial cells regulatevascular endothelial growth factor secretion rates in health anddisease

摘要

Purpose: Choroidal neovascularization (CNV) is the most severecomplication in age-related macular degeneration. The major angiogenicfactor involved is vascular endothelial growth factor (VEGF) secreted bythe retinal pigment epithelium (RPE). Since RPE cells expressneuroendocrine L-type Ca2+ channels we investigated theirinvolvement in VEGF secretion in normal RPE cells and RPE cells frompatients with CNV.Methods: Freshly isolated and cultured RPE cells were studied usingthe patch-clamp technique and ELISA-based secretion assays.Results: Both freshly isolated and cultured cells showed whole-cellBa2+ currents with properties of L-type Ca2+ currents: highactivation threshold, sensitivity to dihydropyridines (10 μMnifedipine) and slow inactivation. VEGF-A secretion was elevated byBayK8644 (10 μM) or basic fibroblast growth factor (bFGF, 10 ng/ml),both of which are able to activate L-type channels. Cells from CNVtissue also showed nifedipine-sensitive Ba2+ currents, whichdisplayed a voltage-dependent activation at more negative potentials,faster inactivation and changed regulation by tyrosine kinasepp60c-src. The CNV RPE cells showed higher VEGF secretion rateswhich were reduced by nifedipine.Conclusions: Thus, L-type Ca2+ channels in normal RPE cellsregulate the secretion of VEGF. RPE cells from eyes with CNV maintain aVEGF secretion regulated by nifedipine-sensitve Ca2+ channelswhich might be of importance for the development of CNV.