Figure 1.

The bioactivity of proliferative vitreoretinopathy (PVR) vitreous depends on three classes of growth factors: vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and non-PDGFs (growth factors outside of the PDGF family). The scheme shows the functional relationship for these growth factors and the signaling events and cellular responses triggered by indirectly activated PDGFRα. VEGF competitively inhibits PDGF-dependent activation of PDGFRα. This direct mode of activating PDGFRα antagonizes the indirect mode of activating PDGFRα, which is driven by non-PDGFs. Indirectly activated PDGFRα promotes TP53 reduction, a key event in driving PVR, because TP53 suppression promotes the viability of cells displaced into the vitreous and also mediates the contraction of PVR membranes formed from these cells; both outcomes are likely to contribute to retinal detachment.¹⁸