title: Attenuation of human lens epithelial cell spreading, migration and contraction via downregulation of the PI3K/Akt pathway.
abstract: BACKGROUND
  Posterior capsule opacification (PCO) represents a major challenge in the postoperative management of cataract patients. Spreading, migration and contraction of residual human lens epithelial cells play a pivotal role in the pathogenesis of PCO. Therefore, we analyzed the effect of the alkylphosphocholine (APC) erufosine on these cellular features as well as on PI3K/Akt, a crucial pathway in PCO pathogenesis.
  
  
  METHODS
  Human lens epithelial cells were cultured under standard cell culture conditions. Cell spreading was analyzed on fibronectin-coated wells and chemokinetic migration was assessed by time-lapse microscopy. For evaluation of cell-mediated collagen matrix contraction, the cells were seeded into collagen gels and incubated with an APC in different non-toxic concentrations before the surface area was measured on day 6. The activity of PI3K/Akt was assessed by an ELISA kit after incubation of the cells with different APC concentrations.
  
  
  RESULTS
  Human lens epithelial cell spreading and migration were attenuated by APCs as follows: 7 % spreading, 48 % migration (0.1 μM APC), and 32 % spreading, 68 % migration (1.0 μM APC). APC concentrations of 0.1 μM reduced collagen gel diameter by 5 %, and 1.0 μM by less than 1 %, compared to untreated, cell-populated gels that resulted in a cell diameter contraction of 36 %. PI3K was downregulated in a concentration-dependent manner.
  
  
  CONCLUSIONS
  The crucial cellular features of PCO pathogenesis are attenuated by the APC erufosine via downregulation of the PI3K pathway. Thus, erufosine might become a valuable tool for pharmacologic PCO prophylaxis in the future.
authors.affiliation: Department of Ophthalmology, Ludwig-Maximilians-University, Mathildenstrasse 8, 80336, Munich, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Liegl
authors.forename: C
authors.initials: C
authors.lastname: Wertheimer
authors.forename: M
authors.initials: M
authors.lastname: Kernt
authors.forename: D
authors.initials: D
authors.lastname: Docheva
authors.forename: A
authors.initials: A
authors.lastname: Kampik
authors.forename: K H
authors.initials: KH
authors.lastname: Eibl-Lindner
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D058442:Capsule Opacification / Q000473:pathology; D002455:Cell Division / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007908:Lens, Crystalline / Q000378:metabolism / Q000473:pathology*; D008954:Models, Biological; D010755:Organophosphates / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D057852:Posterior Capsule of the Lens / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D059008:Time-Lapse Imaging; D054457:Tissue Scaffolds
chemical_list: D000970:Antineoplastic Agents; D010755:Organophosphates; D000644:Quaternary Ammonium Compounds; C472787:erucylphospho-N,N,N-trimethylpropylammonium; D003094:Collagen; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt