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Lasse Joergensen Cehofski, Anders Kruse, Sigridur Olga Magnusdottir, Allan stensballe, Bent honoré, Henrik Vorum; Retinal Proteomics: Protein Changes in Porcine Retinas Following Experimental BRVO and Ranibizumab Intervention. Invest. Ophthalmol. Vis. Sci. 2016;57(12):1753.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal proteins involved in focal adhesion and extracellular matrix remodeling have recently been shown to be upregulated in experimental branch retinal vein occlusion (BRVO). We hypothesized that the expression of a subset of these proteins would be blocked by inhibition of VEGF-A after experimental BRVO.
In five Danish Landrace pigs experimental BRVO was induced in both eyes with an argon laser by applying laser burns onto a branch vein in the inferior retina (Danish Animal Experiments Inspectorate permission 2013-15-2934-00775). After 24 hours an intravitreal injection of 0.05 ml Ranibizumab was administered in the right eyes of the animals while left eyes were given an intravitreal injection of 0.05 ml 0.9% sodium chloride water. Three days after BRVO the retinas were excised and prepared for liquid chromatography tandem mass spectrometry by a filter-aided sample preparation method. In MaxQuant mass spectrometry data were searched against a pig protein database with a peptide and protein false discovery rate of 1%. In Perseus the proteins were filtered requiring at least 2 unique peptides per protein. A two-tailed paired t-test was used for statistic analysis.
In retinas treated with Ranibizumab the analysis identified 29 significantly upregulated proteins (p < 0.05, fold change > 1.25) and 86 significantly downregulated proteins (p < 0.05, fold change < 0.80). Bioinformatic analysis showed a downregulation of proteins involved in cell adhesion including integrin β-1, nectin-2, nidogen-2, protocadherin 7, contactin associated protein 1 and transmembrane glycoprotein NMB. Significantly downregulated proteins also included lipocalin-7 and platelet derived growth factor receptor-β. KEGG pathway analysis identified a downregulation of pathways involved in protein processing in endoplasmic reticulum, cell adhesion and adherens junction.
Integrin-β1, nidogen-2 and lipocalin-7 were downregulated in retinas treated with Ranibizumab. In an earlier study these proteins were found to be upregulated when porcine retinas with experimental BRVO were compared to controls. Therefore, we propose the hypothesis that experimental BRVO is associated with an upregulation of integrin-β1, nidogen-2 and lipocalin-7 that is reversed through intervention with Ranibizumab.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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