PDGFRβ plays an essential role in patient vitreous-stimulated contraction of retinal pigment epithelial cells from epiretinal membranes

Exp Eye Res. 2020 Aug:197:108116. doi: 10.1016/j.exer.2020.108116. Epub 2020 Jun 16.

Abstract

Platelet-derived growth factor (PDGF) is associated with clinical proliferative vitreoretinopathy (PVR), which is characterized by formation of sub- or epi-retinal membranes that consist of cells including retinal pigment epithelial (RPE) cells and extracellular matrix. RPE cells play an important role in PVR pathogenesis. Previous findings indicated that PDGF receptor (PDGFR)α was essential in experimental PVR induced by fibroblasts. In RPE cells derived from epiretinal membranes from patients with PVR (RPEMs), Akt was activated by PDGF-B but not PDGF-A, which suggested that PDGFRβ was the predominant PDGFR isoform expressed in RPEMs. Indeed, CRISPR/Cas9-mediated depletion of PDGFRβ in RPEMs attenuated patient vitreous-induced Akt activation and cellular responses intrinsic to PVR including cell proliferation, migration, and contraction. We conclude that PDGFRβ appears to be the PVR relevant PDGFR isoform in RPEMs.

Keywords: Akt; Contraction; Migration; PDGFRβ; Proliferation; Proliferative vitroretinopathy; RPE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • DNA / genetics*
  • DNA / metabolism
  • Epiretinal Membrane / genetics*
  • Epiretinal Membrane / metabolism
  • Epiretinal Membrane / pathology
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Gene Expression Regulation*
  • Humans
  • Receptor, Platelet-Derived Growth Factor beta / biosynthesis
  • Receptor, Platelet-Derived Growth Factor beta / genetics*
  • Retinal Pigment Epithelium / metabolism*
  • Retinal Pigment Epithelium / pathology

Substances

  • DNA
  • Receptor, Platelet-Derived Growth Factor beta