Retinal proteome changes following experimental branch retinal vein occlusion and intervention with ranibizumab. 2016

Lasse Jørgensen Cehofski, and Anders Kruse, and Martin Bøgsted, and Sigriður Olga Magnusdottir, and Allan Stensballe, and Bent Honoré, and Henrik Vorum
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.

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.

UI MeSH Term Description Entries
D012160 Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the OPTIC NERVE and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the CHOROID and the inner surface with the VITREOUS BODY. The outer-most layer is pigmented, whereas the inner nine layers are transparent. Ora Serrata
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D000069579 Ranibizumab A recombinant humanized monoclonal antibody fragment that binds VEGF-A to prevent its binding to VEGFR-1 and VEGFR-2 receptors. This activity reduces vessel permeability and angiogenesis in the treatment of neovascular age-related MACULAR DEGENERATION. Lucentis,RhuFab V2,V2, RhuFab
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012170 Retinal Vein Occlusion Blockage of the RETINAL VEIN. Those at high risk for this condition include patients with HYPERTENSION; DIABETES MELLITUS; ATHEROSCLEROSIS; and other CARDIOVASCULAR DISEASES. Branch Retinal Vein Occlusion,Branch Vein Occlusion,Central Retinal Vein Occlusion,Retinal Branch Vein Occlusion,Thrombosis, Retinal Vein,Retinal Vein Thrombosis,Branch Vein Occlusions,Occlusion, Branch Vein,Occlusion, Retinal Vein,Retinal Vein Occlusions,Retinal Vein Thromboses,Vein Occlusion, Branch,Vein Occlusion, Retinal,Vein Thrombosis, Retinal
D012269 Ribosomal Proteins Proteins found in ribosomes. They are believed to have a catalytic function in reconstituting biologically active ribosomal subunits. Proteins, Ribosomal,Ribosomal Protein,Protein, Ribosomal
D013552 Swine Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA). Phacochoerus,Pigs,Suidae,Warthogs,Wart Hogs,Hog, Wart,Hogs, Wart,Wart Hog
D014792 Visual Acuity Clarity or sharpness of OCULAR VISION or the ability of the eye to see fine details. Visual acuity depends on the functions of RETINA, neuronal transmission, and the interpretative ability of the brain. Normal visual acuity is expressed as 20/20 indicating that one can see at 20 feet what should normally be seen at that distance. Visual acuity can also be influenced by brightness, color, and contrast. Acuities, Visual,Acuity, Visual,Visual Acuities
D042461 Vascular Endothelial Growth Factor A The original member of the family of endothelial cell growth factors referred to as VASCULAR ENDOTHELIAL GROWTH FACTORS. Vascular endothelial growth factor-A was originally isolated from tumor cells and referred to as "tumor angiogenesis factor" and "vascular permeability factor". Although expressed at high levels in certain tumor-derived cells it is produced by a wide variety of cell types. In addition to stimulating vascular growth and vascular permeability it may play a role in stimulating VASODILATION via NITRIC OXIDE-dependent pathways. Alternative splicing of the mRNA for vascular endothelial growth factor A results in several isoforms of the protein being produced. Vascular Endothelial Growth Factor,Vascular Endothelial Growth Factor-A,GD-VEGF,Glioma-Derived Vascular Endothelial Cell Growth Factor,VEGF,VEGF-A,Vascular Permeability Factor,Vasculotropin,Glioma Derived Vascular Endothelial Cell Growth Factor,Permeability Factor, Vascular
D058449 Intravitreal Injections The administration of substances into the VITREOUS BODY of the eye with a hypodermic syringe. Injection, Intravitreal,Injections, Intravitreal,Intravitreal Injection

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