title: The effects of aflibercept on the viability and metabolism of ocular cells in vitro.
abstract: OBJECTIVE
  To investigate the effects of the vascular endothelial growth factor-neutralizing agent aflibercept on primary cultures of human trabecular meshwork cells (hTMC), human scleral fibroblasts (hFibro), and a retinal pigment epithelial cell line (ARPE-19).
  
  
  METHODS
  Various concentrations of aflibercept were incubated with confluent cell cultures for 24 hours. Ranibizumab was used as an active control for comparison. Assays of cellular metabolism (MTT assay) and cell viability (calcein dye uptake) were performed.
  
  
  RESULTS
  Compared with untreated controls (100% live), a 24-hour exposure to 1 mg/mL aflibercept had no significant effect on cell viability in hTMC (100.1 ± 1.7%), hFibro (102.4 ± 2.4%), or ARPE-19 (99.3 ± 3.9%) cells. Aflibercept vehicle controls also had no detrimental effect. Aflibercept (1 mg/mL) had no statistically significant effect on metabolic activity in hTMC (84.3 ± 10.2%), hFibro (102.7 ± 4.3%), and ARPE-19 (104.6 ± 12.6%) cells. When compared side-by-side in ARPE-19 cells, aflibercept and the anti-vascular endothelial growth factor agent ranibizumab had no toxicity at the highest concentration tested (1 mg/mL).
  
  
  CONCLUSIONS
  The authors' data reveal that concentrations of aflibercept in the range expected to occur in the human vitreous after intraocular injection are not harmful in an in vitro cell assay.
authors.affiliation: Department of Ophthalmology, University of Colorado School of Medicine, Aurora, Colorado 80045, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Ammar
authors.forename: Naresh
authors.initials: N
authors.lastname: Mandava
authors.forename: Malik Y
authors.initials: MY
authors.lastname: Kahook
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D040262:Receptors, Vascular Endothelial Growth Factor / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012590:Sclera / Q000166:cytology / Q000378:metabolism; D014129:Trabecular Meshwork / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D020533:Angiogenesis Inhibitors; D011993:Recombinant Fusion Proteins; D042461:Vascular Endothelial Growth Factor A; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor