Expression of PDGFR?± Is a Determinant of the PVR Potential of ARPE19 Cells

摘要

Purpose.: Previous studies indicate that the expression of platelet-derived growth factor (PDGF) receptor ?± (PDGFR?±) dramatically increases the ability of fibroblasts to induce experimental proliferative vitreoretinopathy (PVR). The purpose of this study was to determine whether PDGFR?± contributed to the PVR potential of retinal pigment epithelial (RPE) cells, one of the most abundant cell types in PVR membranes. Methods.: PDGFR?± expression in human ARPE19 cells was increased or decreased by stably expressing the PDGFR?± cDNA or short hairpin (sh) RNA directed at PDGFR?±, respectively. The level of PDGFR?± expression in the resulting panel of cell lines was either barely detectable (KD), standard (similar to the level of primary RPE cells), or overexpressed approximately 80-fold. Western blot analysis was used to assess the level of p53 and the activation state of PDGFR?± and Akt. The following cellular responses were monitored: proliferation, apoptosis, and contraction. The PVR potential of cells was tested in a rabbit model of PVR in which cells were coinjected with platelet-rich plasma into the vitreous. Results.: Comparison of KD and overexpressing cells indicated that high-level expression of PDGFR?± dramatically augmented signaling events, cellular responses, and the PVR potential of ARPE19 cells. However, all these outcomes were also significantly increased, albeit not as robustly, by PDGFR?± expression to the level typically present in RPE cells. Conclusions.: Even though RPE cells express substantially less PDGFR?± than fibroblasts, it significantly boosts PVR-related signaling events, cellular responses, and the PVR potential of ARPE19 cells. These studies suggest that inhibiting activation, signaling, or both by PDGFR?± has the potential to prevent the development of PVR.