title: Response to anti-VEGF-A treatment of retinal pigment epithelial cells in vitro.
abstract: OBJECTIVE
  The neovascular or wet form of age-related macular degeneration is characterized by the growth of abnormal blood vessels in the retina stimulated by vascular endothelial growth factors (VEGF). In the last decade, several anti-VEGF drugs have been developed for treating neovascular diseases of the eyes. This study was conducted to compare the effects of 2 anti-VEGF-A drugs, ranibizumab and aflibercept, on the expression and secretion of VEGF family members in retinal pigment epithelial cells (RPE) in vitro.
  
  
  METHODS
  ARPE-19 cells were exposed for 24 hours to ranibizumab or aflibercept at clinical dose concentration. Cell viability and expression and secretion of VEGF-A, VEGF-B, VEGF-C, and placental growth factor (PlGF) were evaluated respectively by real-time polymerase chain reaction and enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Ranibizumab and aflibercept did not affect ARPE-19 cell viability after 24 hours of treatment. Ranibizumab increased expression of VEGF-A and PlGF. On the contrary, expression and secretion of VEGF-C was decreased by ranibizumab. PlGF secretion was not affected by ranibizumab. Aflibercept strongly increased VEGF-A and PlGF expression but reduced their detection on the culture media, and decreased expression and secretion of VEGF-C. No effect on expression and secretion of VEGF-B was observed after exposure to these drugs.
  
  
  CONCLUSIONS
  Ranibizumab and aflibercept exert similar effects on VEGF expression and secretion, leading to establishing an antiangiogenic environment. Increased VEGF-A expression observed in RPE cells treated with these drugs suggests a compensatory response of the cells to the lack of VEGF-A.
authors.affiliation: Department of Internal Medicine and Medical Specialties, Genova - Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Puddu
authors.affiliation: Department of Internal Medicine and Medical Specialties, Genova - Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Sanguineti
authors.affiliation: Department of Neuroscience, Ophthalmology and Genetics, Genova - Italy.
authors.forename: Carlo Enrico
authors.initials: CE
authors.lastname: Traverso
authors.affiliation: Department of Internal Medicine and Medical Specialties, Genova - Italy.
authors.forename: Giorgio L
authors.initials: GL
authors.lastname: Viviani
authors.affiliation: Department of Neuroscience, Ophthalmology and Genetics, Genova - Italy.|Fondazione per la Macula onlus, Genova - Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Nicolò
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008268:Macular Degeneration / Q000188:drug therapy; D000072483:Placenta Growth Factor / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D000069579:Ranibizumab / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D040262:Receptors, Vascular Endothelial Growth Factor; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D055213:Retinal Pigment Epithelium / Q000187:drug effects* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000235:genetics
chemical_list: D020533:Angiogenesis Inhibitors; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000072483:Placenta Growth Factor; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor; D000069579:Ranibizumab