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H. Lei, G. Velez, A. Kazlauskas; The Role of Growth Factors Outside of the PDGF Family in Experimental Proliferative Vitreoretinopathy. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4896. doi: https://doi.org/.
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Proliferative vitreoretinopathy (PVR) is a major cause of failure of retinal reattachment surgery. Surgical intervention is the only treatment option, and does not achieve anatomical success is 20-40% of the patients. Consequently, there is an acute need to identify the molecular mediators of PVR. Platelet-derived growth factor (PDGF), especially the PDGF-C isoform, and PDGF receptors (PDGFRs) are associated with both experimental and clinical PVR. However, preliminary studies have shown that neutralizing PDGF-C did not prevent experimental PVR. The purpose of this study was to investigate how PDGFR promoted experimental PVR in an apparently PDGF-independent manner.
Activation of the PDGFR was monitored by immunoprecipitating the PDGFR from lysates of resting or activated retinal pigment epithelial (RPE) cells and subjecting it to anti-phosphotyrosine Western blotting. Association of phosphoinositide 3 kinase (PI3K) with the PDGFR was determined by coimmunoprecipitation of the p85 subunit of PI3K with the PDGFR. Activation of Akt and Erk was determined by Western blot analysis of total cell lysates using the appropriate phospho-specific Akt and Erk antibodies.
A number of growth factors outside of the PDGF family (EGF, bFGF, HGF and insulin) activated the PDGFR and induced its association with PI3K. Expression of the PDGFR in RPE cells potentiated the signaling of non-PDGFs via Akt and Erk. The underlying mechanism leading to Akt activation was at least in part due to tyrosine phosphorylation of the PDGFR at residues necessary for recruitment and activation of PI3K.
Expression of the PDGFR potentiated the responsiveness of RPE cells to growth factors outside of the PDGF family. This observation offers an explanation for how experimental PVR could be dependent on PDGFR, yet independent of PDGF. Furthermore, these findings identify the PDGFR as a particularly attractive pharmacological target for PVR.
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