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A. Kazlauskas, H. Lei, G. Velez; Growth Factors Outside of the Pdgf Family Drive Experimental Pvr. Invest. Ophthalmol. Vis. Sci. 2009;50(13):6227.
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Proliferative vitreoretinopathy (PVR) is a recurring and problematic disease for which there is no pharmacological treatment. There is a striking association between PVR and the presence of vitreal platelet-derived growth factor (PDGF) in both experimental and clinical PVR. Furthermore, receptors for PDGF (PDGFR) are present and activated in epiretinal membranes of patient donors. PDGFRs are essential for experimental PVR. Together, these studies suggest that PVR arises at least in part from PDGF/PDGFR driven-events. The goal of this study was to determine if PDGFs were a potential therapeutic target for PVR.
Experimental PVR was induced in rabbits by injecting fibroblasts. Vitreous specimens were collected from experimental rabbits, or from patients undergoing vitrectomy surgery to repair retinal detachment. A neutralizing PDGF antibody and a PDGF Trap were tested for their ability to prevent experimental PVR. Contraction of collagen gels was monitored in vitro. Activation of PDGFR was monitored by anti-phosphotyrosine Western blotting of PDGFR immunoprecipitates.
Neutralizing PDGFs in the vitreous did not effectively attenuate PVR, even though the reagents employed effectively blocked PDGF-dependent activation of the PDGF receptor (PDGFR). Vitreal growth factors outside of the PDGF family modestly activated PDGFR, and appeared to do so without engaging the ligand-binding domain of PDGFR. This indirect route to activate PDGFR had profound functional consequences: it promoted contraction of collagen gels, and appeared sufficient to drive experimental PVR.
While PDGFs appear to be a poor therapeutic target, PDGFR is a particularly attractive one since it can be activated by a much larger spectrum of vitreal growth factors than previously appreciated.
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