The effects of aflibercept on the viability and metabolism of ocular cells in vitro

Retina. 2013 May;33(5):1056-61. doi: 10.1097/IAE.0b013e31827b646d.

Abstract

Purpose: 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).

Conclusion: 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.

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Fibroblasts / drug effects
  • Humans
  • Receptors, Vascular Endothelial Growth Factor / pharmacology*
  • Recombinant Fusion Proteins / pharmacology*
  • Retinal Pigment Epithelium / cytology
  • Retinal Pigment Epithelium / drug effects*
  • Retinal Pigment Epithelium / metabolism
  • Sclera / cytology
  • Sclera / metabolism
  • Trabecular Meshwork / cytology
  • Trabecular Meshwork / drug effects*
  • Trabecular Meshwork / metabolism
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*

Substances

  • Angiogenesis Inhibitors
  • Recombinant Fusion Proteins
  • Vascular Endothelial Growth Factor A
  • aflibercept
  • Receptors, Vascular Endothelial Growth Factor