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S. Peters, S. Radetzky, N. Kociok, B. Kirchhof, A.M. Joussen; Loss of Pericytes and Vessel Destabilization in Corneal Neovascularization after Treatment with PDGF-receptor Inhibitor . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2245.
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Purpose: Neovascularization play a key role in various diseases of the eye, such as corneal neovascularization, diabetes or age-related macular degeneration. Platelet derived growth factor (PDGF) is involved in vessel formation and stabilization, and therefore is a possible target for anti-angiogenic therapy by inhibiting agents. Methods: Corneal neovascularization were induced in C57/Bl6 mice by mechanical removal of the limbal epithelium. 7 days later, when mature vessels were present, mice were treated systemically by a PDGF-receptor beta inhibitor, using an intraperitoneally implanted mini-osmotic pump. 7 days later, corneal flatmounts of treated and untreated (control) mice were prepared after immuno-staining with FITC-CD31 for endothelial cells and Cy3-SMA (smooth muscle actin) for pericytes. VEGF (vascular endothelial growth factor) levels were determined by RT-PCR. Results: Mice treated with PDGF inhibitor showed a significant reduction of pericytes in their corneal neovascularization compared to untreated animals. Whereas in control eyes 63% of the vessel surface was covered with pericytes, it was only 10% in the eyes with PDGF-receptor inhibition. The mean vessel diameter was increased 3.7-fold after PDGF-receptor inhibition. VEGF level was increased 3.6-fold in these eyes. Conclusions: Reduction of pericytes after treatment with PDGF-receptor inhibitor leads to an enlargement of vessel diameter and indicates vessel destabilization. So interestingly the vacularized area was not reduced and VEGF expression was increased. PDGF activates the signal transduction molecules ERK (extracellular signal-regulated kinase)and Akt (protein kinase B) and can activate VEGF expression via these molecules. Since VEGF expression was conversely increased after PDGF inhibition, alternative pathways seem to be involved.
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