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Hetian Lei, Marc-Andre Rheaume, Gisela Velez, Shizuo mukai, Andrius Kazlauskas; Expression Of PDGFRα In Retinal Pigment Epithelial Cells Promotes Experimental Proliferative Vitreoretinopathy. Invest. Ophthalmol. Vis. Sci. 2011;52(14):6590.
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© ARVO (1962-2015); The Authors (2016-present)
Proliferative vitreoretinopathy (PVR) is the major obstacle to successful surgical treatment of rhegmatogenous retinal detachment. Epiretinal membranes from patients with PVR contain a number of cell types: retinal pigment epithelial cells (RPE), retinal glial cells, fibroblasts and macrophages. Previous studies with fibroblasts indicated that expression of platelet-derived growth factor (PDGF) receptor α (PDGFRα) dramatically increased the PVR potential of this cell type. The purpose of this study was to test the following two hypotheses: 1) PDGFRα expression was essential for RPE cells to induce PVR; 2) the level of PDGFRα expression was an important variable: more receptor would increase the severity of PVR.
The level of PDGFRα in human ARPE-19 cells was increased or decreased by stably expressing the PDGFRα cDNA or short hairpin (sh) RNA, respectively. The level of PDGFRα expression in the resulting panel of cell lines was either barely detectable (KD), modest (i.e. similar to the level of primary RPE cells isolated from a donor PVR membrane), or overexpressed approximately 30 fold. Western blotting was used to assess the level of p53 and the activation state of PDGFRα and Akt. The following cell responses were monitored: proliferation, apoptosis and contraction. The PVR potential of cells was tested in a rabbit model of PVR in which cells were co-injected with platelet-rich plasma into the vitreous.
Comparison of KD and overexpressing cells indicated that high level expression of PDGFRα dramatically augmented signaling events, cellular responses and the PVR potential of ARPE-19 cells. All of these outcomes were also significantly increased by only modest expression of PDGFRα. Comparison of cells that expressed a modest versus high level of PDGFRα indicated that overexpressing PDGFRα enhanced signaling events and some of the cellular responses (i.e. cell contraction), but resulted in only a small increase in the PVR potential of the cells.
Like fibroblasts, the PVR potential of RPE cells was dependent on expression of PDGFRα. A modest level of expression was sufficient to significantly boost PVR-related signaling events, cellular responses and the PVR potential of ARPE-19 cells. These studies suggest that preventing activation and/or signaling by PDGFRα has the potential to prevent the most sight-threatening components of PVR.
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