Cordeiro, Soenke and Seyler, Sebastian and Stindl, Julia and Milenkovic, Vladimir M. and Strauss, Olaf (2010) Heat-Sensitive TRPV Channels in Retinal Pigment Epithelial Cells: Regulation of VEGF-A Secretion. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 51 (11). pp. 6001-6008. ISSN 0146-0404, 1552-5783
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PURPOSE. Choroidal neovascularization in age-related macular degeneration is caused, to a large extent, by increased secretion of vascular endothelial growth factor (VEGF)-A by the retinal pigment epithelium (RPE). The purpose of the study was to identify pathways that lead to increased VEGF secretion by the RPE. METHODS. Ca2(+) signaling was studied in ARPE-19 and human RPE cells in primary culture by means of Ca2(+) imaging. Membrane conductance was measured in the whole-cell configuration of the patch-clamp technique. VEGF-A secretion was measured by using ELISA. RESULTS. Freshly isolated RPE cells or ARPE-19 cells were shown to express TRPV1, -2, -3, and -4 channels. Increasing the temperature or stimulation by IGF-1 increased the VEGF-A secretion rate in both cell types. These effects were both sensitive to the TRPV channel blocker ruthenium red (20 mu M). The heat-inducible Ca2(+) signals were blocked by the TRPV channel blockers La3(+) and ruthenium red by 68% and 52%, respectively. In contrast, high concentrations of 2-APB (3 mM) increased [Ca2(+)](i), whereas the TRPV1 channel opener capsaicin and the TRPV3 channel opener camphor had no effect. Reduction of TRPV2 expression by siRNA attenuated the heat-evoked Ca2(+) response. In addition, a heat-activated inwardly rectifying current was measured that was completely blocked by ruthenium red. IGF-1 also increased whole-cell current with a corresponding increase in [Ca2(+)](i), which was blocked by the PI3-kinase blocker LY294002. CONCLUSIONS. The data strongly suggest that TRPV2 channels expressed by the RPE are involved in the Ca2(+) signaling that mediates both heat-dependent and IGF-1 (via PI3-kinase activation)-induced VEGF secretion. (Invest Ophthalmol Vis Sci.2010;51:6001-6008) DOI:10.1167/iovs.09-4720
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ENDOTHELIAL GROWTH-FACTOR; AGE-RELATED MACULOPATHY; CHOROIDAL BLOOD-FLOW; MACULAR DEGENERATION; FACTOR-I; TRANSPUPILLARY THERMOTHERAPY; IGFBP-3 SECRETION; UP-REGULATION; ION CHANNELS; FACTOR-BETA; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Augenheilkunde |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 Jul 2020 08:41 |
| Last Modified: | 07 Jul 2020 08:41 |
| URI: | https://pred.uni-regensburg.de/id/eprint/23950 |
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