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J.A. Weissmann, S. Ehmer, A. Eggers, T. Lischka, S. Wimmers, O. Strauss; Induction of VEGF–A Secretion via an Autocrine Feed–Back–Loop . Invest. Ophthalmol. Vis. Sci. 2005;46(13):5366.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: A most severe complication of the exudative form of age–related macular degeneration is the choroidal neovascularization (CNV). The most important angiogenic factor for this neovascularization is the vascular endothelial growth factor–A (VEGF–A). A major portion of VEGF–A is released by the retinal pigment epithelium (RPE). In addition to their expression in the endothelium of the choroidal vessels, all three known VEGF receptors are expressed by the RPE itself. The purpose of this study was to get insight into the regulation of VEGF–A secretion by RPE cells. Methods: The secretion of VEGF–A was measured in confluent cultures of ARPE–19 cells using a sandwich ELISA. The expression pattern of the components of the VEGF signalling was investigated by RT–PCR. Results: The RT–PCR showed that the VEGF family members VEGF–A, –B, –C, and the placenta groth factor (PlGF) – an additional ligand of VEGF receptors – are expressed in the RPE. The VEGF receptor Flt–1 (VEGFR–1) was activated by the application of PlGF, and KDR (VEGFR–2) and/or Flt–4 (VEGFR–3) by VEGF–C. Both substances were able to induce an increased VEGF–A secretion. The activation of Flt–1 led to an 2.4–fold increase of the VEGF–A secretion 8 hours after stimulation, whereas the activation of KDR and/or Flt–4 increased the VEGF–A secretion 1.6–fold. Conclusions: We have shown for the first time that the stimulation of different VEGF receptors on RPE cells induce increased VEGF–A secretion. Since mediators for the activation of all three VEGF receptors are expressed by the RPE itself (PlGF, VEGF–A and –B for Flt–1, VEGF–A and –C for KDR, and VEGF–C for Flt–4), we suggest an autocrine feed–back–loop for the VEGF–A secretion.
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