Proteome Analysis of Aflibercept Intervention in Experimental Central Retinal Vein Occlusion

Lasse Jørgensen Cehofski*, Anders Kruse, Alexander Nørgaard Alsing, Benn Falch Sejergaard, Jonas Ellegaard Nielsen, Anders Schlosser, Grith Lykke Sorensen, Jakob Grauslund, Bent Honoré, Henrik Vorum

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

5 Citations (Scopus)
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Aflibercept is a frequently used inhibitor of vascular endothelial growth factor (VEGF) in the treatment of macular edema following central retinal vein occlusion (CRVO). Retinal proteome changes following aflibercept intervention in CRVO remain largely unstudied. Studying proteomic changes of aflibercept intervention may generate a better understanding of mechanisms of action and uncover aspects related to the safety profile. In 10 Danish Landrace pigs, CRVO was induced in both eyes with an argon laser. Right eyes were treated with intravitreal aflibercept while left control eyes received isotonic saline water. Retinal samples were collected 15 days after induced CRVO. Proteomic analysis by tandem mass tag-based mass spectrometry identified a total of 21 proteins that were changed in content following aflibercept intervention. In retinas treated with aflibercept, high levels of aflibercept components were reached, including the VEGF receptor-1 and VEGF receptor-2 domains. Fold changes in the additional proteins ranged between 0.70 and 1.19. Aflibercept intervention resulted in a downregulation of pigment epithelium-derived factor (PEDF) (fold change = 0.84) and endoplasmin (fold change = 0.91). The changes were slight and could thereby not be confirmed with less precise immunohistochemistry and Western blotting. Our data suggest that aflibercept had a narrow mechanism of action in the CRVO model. This may be an important observation in cases when macular edema secondary to CRVO is resistant to aflibercept intervention.

Original languageEnglish
Article number3360
Issue number11
Publication statusPublished - 1 Jun 2022


  • Angiogenesis Inhibitors/pharmacology
  • Animals
  • Intravitreal Injections
  • Macular Edema/complications
  • Proteome
  • Proteomics
  • Receptors, Vascular Endothelial Growth Factor
  • Recombinant Fusion Proteins/pharmacology
  • Retinal Vein Occlusion/complications
  • Swine
  • Vascular Endothelial Growth Factor A
  • Visual Acuity
  • proteomics
  • aflibercept
  • retinal vein occlusion
  • proteome
  • retina
  • vascular endothelial growth factor
  • mass spectrometry


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