title: EGFR inhibitor Gefitinib attenuates posterior capsule opacification in vitro and in the ex vivo human capsular bag model.
abstract: OBJECTIVE
  Posterior capsule opacification (PCO) occurs as a common complication after cataract surgery. Gefitinib is a selective inhibitor of the epidermal growth factor receptor (EGFR) which represents a potential pharmacological target for PCO prevention. In this in vitro study, we assessed the effect and biocompatibility of Gefitinib in PCO prophylaxis.
  
  
  METHODS
  The effect of Gefitinib on the key pathological features of PCO was assessed in vitro. We determined growth in the human capsular bag model, prepared from sixteen cadaver eyes that underwent sham cataract surgery. Furthermore, two lens epithelial cell lines, HLE-B3 and FHL-124, were used to determine concentration-based effects on cell proliferation. In addition, cell-migration, matrix-contraction, and cell spreading were investigated. To exclude toxic concentrations, Gefitinib was assessed for its biocompatibility on six different human ocular cell types from the anterior and posterior segment of the eye.
  
  
  RESULTS
  Gefitinib significantly increased the time until confluence of the capsular bag compared to controls (p < 0.001)). In both human lens epithelial cell lines (HLE-B3 and FHL-124), proliferation decreased significantly and as equally strong after incubation with Gefitinib (p < 0.001), as did chemotactic migration (p = 0.004), matrix contraction (p = 0.001), and cell-spreading (p = 0.001). At the IC50 concentration, Gefitinib was well tolerated by six different human ocular cell types of the anterior and posterior segment.
  
  
  CONCLUSIONS
  The specific EGFR inhibitor Gefitinib might become of clinical relevance in PCO prophylaxis as it attenuated cellular growth and other pathological PCO factors in the ex vivo human capsular bag model and in two human lens epithelial cell lines, while showing good biocompatibility in vitro.
authors.affiliation: Department of Ophthalmology, Ludwig-Maximilians-University, Mathildenstrasse 8, 80336, Munich, Germany, Christian.Wertheimer@med.uni-muenchen.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Wertheimer
authors.forename: Jakob
authors.initials: J
authors.lastname: Siedlecki
authors.forename: Daniel
authors.initials: D
authors.lastname: Kook
authors.forename: Wolfgang J
authors.initials: WJ
authors.lastname: Mayer
authors.forename: Armin
authors.initials: A
authors.lastname: Wolf
authors.forename: Annemarie
authors.initials: A
authors.lastname: Klingenstein
authors.forename: Anselm
authors.initials: A
authors.lastname: Kampik
authors.forename: Kirsten
authors.initials: K
authors.lastname: Eibl-Lindner
mesh_terms: D000328:Adult; D000368:Aged; D058442:Capsule Opacification / Q000517:prevention & control*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D000077156:Gefitinib; D006801:Humans; D007908:Lens, Crystalline / Q000166:cytology; D008422:Materials Testing; D008875:Middle Aged; D009457:Neuroglia / Q000187:drug effects; D057852:Posterior Capsule of the Lens / Q000187:drug effects*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*; D055213:Retinal Pigment Epithelium / Q000187:drug effects
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib