TY - JOUR
T1 - Proteome Analysis of Aflibercept Intervention in Experimental Central Retinal Vein Occlusion
AU - Cehofski, Lasse Jørgensen
AU - Kruse, Anders
AU - Alsing, Alexander Nørgaard
AU - Sejergaard, Benn Falch
AU - Nielsen, Jonas Ellegaard
AU - Schlosser, Anders
AU - Sorensen, Grith Lykke
AU - Grauslund, Jakob
AU - Honoré, Bent
AU - Vorum, Henrik
PY - 2022/6/1
Y1 - 2022/6/1
N2 - 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.
AB - 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.
KW - Angiogenesis Inhibitors/pharmacology
KW - Animals
KW - Intravitreal Injections
KW - Macular Edema/complications
KW - Proteome
KW - Proteomics
KW - Receptors, Vascular Endothelial Growth Factor
KW - Recombinant Fusion Proteins/pharmacology
KW - Retinal Vein Occlusion/complications
KW - Swine
KW - Vascular Endothelial Growth Factor A
KW - Visual Acuity
KW - proteomics
KW - aflibercept
KW - retinal vein occlusion
KW - proteome
KW - retina
KW - vascular endothelial growth factor
KW - mass spectrometry
UR - http://www.scopus.com/inward/record.url?scp=85130525319&partnerID=8YFLogxK
U2 - 10.3390/molecules27113360
DO - 10.3390/molecules27113360
M3 - Journal article
C2 - 35684299
SN - 1420-3049
VL - 27
JO - Molecules
JF - Molecules
IS - 11
M1 - 3360
ER -