title: PI3K/AKT/mTOR signaling pathway inhibitors in proliferation of retinal pigment epithelial cells.
abstract: OBJECTIVE
  To determine whether the PI3K/AKT/mTOR pathway is activated in proliferative vitreoretinopathy (PVR) in homo-sapiens.
  
  
  METHODS
  The retina of controls and patients with PVR were collected and their levels of PI3K, phospho-AKT, phospho-mTOR, phospho-p70S6k and phospho-4EBP-1 were determined by Western blot. The cultured human retinal pigment epithelial cell line D407 was treated with a specific mTOR inhibitor, rapamycin (RAPA) or a PI3K inhibitor, LY294002, of various concentrations and durations. Cell morphology was observed by phase contrast microscopy and the proliferation and apoptosis of treated cells were determined by MTT assay and flow cytometry.
  
  
  RESULTS
  Levels of PI3K, phospho-AKT, phospho-mTOR, phospho-P70S6K and phospho-4EBP1 was increased in the retina in PVR (P<0.05). In D407 cells, both RAPA and LY294002 significantly inhibited cell proliferation and cell cycle progression, and promoted apoptosis (P <0.05); morphologically, the cells became smaller. Both RAPA and LY294002 reduced levels of phospho-AKT, phospho-mTOR, phospho-p70S6k and phospho-4EBP1 expression (P <0.05). RAPA, but not LY294002, had no significant effect on PI3K expression.
  
  
  CONCLUSIONS
  PI3K/AKT/mTOR signaling pathway is highly activated in the retinal pigment epithelial cells of PVR. The inhibitors of PI3K/AKT/mTOR signaling pathway, RAPA and LY294002, could inhibited the PI3K/AKT/mTOR signaling pathway by reducing the levels of phosphorylation of mTOR pathway components.
authors.affiliation: Department of Ophthalmology, the First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China.
authors.forename: Na
authors.initials: N
authors.lastname: Cai
authors.forename: Shun-Dong
authors.initials: SD
authors.lastname: Dai
authors.forename: Ning-Ning
authors.initials: NN
authors.lastname: Liu
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Liu
authors.forename: Ning
authors.initials: N
authors.lastname: Zhao
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
keywords: PI3K/AKT/mTOR signal pathway; human retinal pigment epithelial cell; proliferative vitreoretinopathy