Expression of PDGFRα Is a Determinant of the PVR Potential of ARPE19 Cells

Proliferative vitreoretinopathy (PVR) is a disorder characterized by the formation of membranes on both surfaces of the retina that contract and thereby induce retinal detachment. PVR results from various causes, but it is most often encountered after retinal tears and retinal detachment and after therapeutic interventions for these conditions. It occurs in approximately 8% to 10% of patients undergoing primary retinal detachment surgery and is the principal cause of failure of this procedure.1–5 The PVR membrane consists of extracellular matrix proteins (collagen I and II and fibronectin), and cells (retinal pigment epithelial cells [RPE], retinal glial cells, fibroblasts, and macrophages).6–9 RPE cells are among the most abundant cell type in PVR membranes, and this probably relates to the retinal break and dispersion of viable RPE cells into the vitreous during cryopexy treatment of retinal tears.10–12 Although there has been increased success in reattaching the retina, understanding the molecular mechanism of PVR is likely to enable the development of effective pharmacologic approaches to protect patients undergoing surgery to correct a retinal detachment from succumbing to PVR. Results of recent studies support the growth factor hypothesis regarding the pathogenesis of PVR.13 For instance, growth factors are present in the vitreous and promote many of the cellular events that are intrinsic to PVR. Furthermore, the expression of platelet-derived growth factor (PDGF) receptor α (PDGFRα) increases the ability of fibroblasts to induce experimental PVR.14 Moreover, blocking growth factor-dependent activation of receptors or the downstream signaling events protects animals from developing experimental PVR.15–18 These studies begin to elucidate key events in the development of PVR and thereby identify potential therapeutic targets. A potential shortcoming of the information obtained using a fibroblast-driven model of PVR is that fibroblasts are not the major cell type within clinical PVR membranes. Consequently, the goal of this study was to identify an Achilles heel in RPE cells, one of the most abundant cell types within clinical PVR membranes. In light of the fact that cultured RPE cell lines express PDGFRα19 and that this receptor is expressed and activated in PVR membranes isolated from patients,20,21 we focused on evaluating the importance of PDGFRα for RPE cells to induce experimental PVR.