Retinal proteome changes following experimental branch retinal vein occlusion and intervention with ranibizumab.
Animal models of experimental branch retinal vein occlusion (BRVO) provide a unique opportunity to study protein changes directly in retinal tissue. Results from these experimental models suggest that experimental BRVO is associated with an upregulation of extracellular matrix remodeling and adhesion signaling processes. To study whether these processes could be blocked by inhibition of VEGF-A, a porcine model of experimental BRVO was combined with proteomic analyses. In six Danish Landrace pigs experimental BRVO was induced with argon laser in both eyes. After 24 h an injection of 0.05 mL ranibizumab was given in the right eyes of the animals while left eyes received an injection of 0.05 mL 9 mg/mL sodium chloride water. Retinas were dissected three days after BRVO and the retinal samples were analyzed with label-free quantification as well as tandem mass tag based proteomics. In retinas treated with ranibizumab five proteins exhibited statistically significant changes in content with both proteomic techniques. These five proteins, which were all decreased in content, included integrin β-1, peroxisomal 3-ketoacyl-CoA thiolase, OCIA domain-containing protein 1, calnexin and 40S ribosomal protein S5. As anti-integrin therapies are under development for inhibition of angiogenesis in retinal diseases it is interesting that inhibition of VEGF-A in itself resulted in a small decrease in the content of integrin β-1. The decreased content of integrin β-1 indicates that extracellular matrix remodeling and adhesion processes associated with BRVO are at least partly reversed through inhibition of VEGF-A.
Department of Ophthalmology, Aalborg University Hospital, Aalborg, Denmark; Biomedical Research Laboratory, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. Electronic address: L.cehofski@rn.dk.
Lasse Jørgensen
LJ
Cehofski
Department of Ophthalmology, Aalborg University Hospital, Aalborg, Denmark.
Anders
A
Kruse
Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Department of Haematology, Aalborg University Hospital, Aalborg, Denmark.
Martin
M
Bøgsted
Biomedical Research Laboratory, Aalborg University Hospital, Aalborg, Denmark.
Sigriður Olga
SO
Magnusdottir
Department of Health Science and Technology, Aalborg University, Denmark.
Allan
A
Stensballe
Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Bent
B
Honoré
Department of Ophthalmology, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
Henrik
H
Vorum
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000818:Animals; D037281:Calnexin / Q000378:metabolism; D004195:Disease Models, Animal; D019012:Integrin beta1 / Q000378:metabolism; D058449:Intravitreal Injections; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D000069579:Ranibizumab / Q000008:administration & dosage*; D012160:Retina / Q000378:metabolism; D012170:Retinal Vein Occlusion / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000378:metabolism; D013552:Swine; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014792:Visual Acuity
D020533:Angiogenesis Inhibitors; D019012:Integrin beta1; D020543:Proteome; D012269:Ribosomal Proteins; D042461:Vascular Endothelial Growth Factor A; C030831:ribosomal protein S5; D037281:Calnexin; D000069579:Ranibizumab
Biological marker; Integrin; Mass spectrometry; Protein; Proteomics; Ranibizumab; Retina; Retinal vein occlusion; Vascular endothelial growth factor