Chalcomoracin prevents vitreous-induced activation of AKT and migration of retinal pigment epithelial cells

J Cell Mol Med. 2021 Oct;25(19):9102-9111. doi: 10.1111/jcmm.16590. Epub 2021 Aug 25.

Abstract

Retinal pigment epithelial (RPE) cells are the major cell type in the epi- or sub-retinal membranes in the pathogenesis of proliferative vitreoretinopathy (PVR), which is a blinding fibrotic eye disease and still short of effective medicine. The purpose of this study is to demonstrate whether Chalocomoracin (CMR), a novel purified compound from fungus-infected mulberry leaves, is able to inhibit vitreous-induced signalling events and cellular responses intrinsic to PVR. Our studies have revealed that the CMR IC50 for ARPE-19 cells is 35.5 μmol/L at 72 hours, and that 5 μmol/L CMR inhibits vitreous-induced Akt activation and p53 suppression; in addition, we have discovered that this chemical effectively blocks vitreous-stimulated proliferation, migration and contraction of ARPE-19 cells, suggesting that CMR is a promising PVR prophylactic.

Keywords: Akt; chalocomoracin; contraction; migration; p53; proliferation; proliferative vitreoretinopathy; vitreous.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzofurans / chemistry
  • Benzofurans / pharmacology*
  • Cell Line
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism*
  • Humans
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Rabbits
  • Retinal Pigment Epithelium / cytology
  • Retinal Pigment Epithelium / metabolism*
  • Signal Transduction / drug effects
  • Tumor Suppressor Protein p53 / metabolism
  • Vitreous Body / metabolism*

Substances

  • Benzofurans
  • Tumor Suppressor Protein p53
  • chalcomoracin
  • Proto-Oncogene Proteins c-akt