Abstract
Purpose :
Retinal proteome changes following treatment with intravitreal dexamethasone implants remain largely unstudied. In an experimental model of branch retinal vein occlusion (BRVO) we studied large-scale retinal protein changes resulting from treatment with Ozurdex implants.
Methods :
In five Danish Landrace pigs experimental BRVO was induced in both eyes by applying argon laser onto a vein in the inferior retina (permission 2016-15-0201-00971). Within 30 minutes after BRVO had been induced, a dexamethasone implant (Ozurdex, purchased from Allergan) was injected into the right eye of each animal. A similar injection without any implant was made in the left eyes that served as controls. BRVO was confirmed by fluorescein angiography. Fifteen days after BRVO the eyes were enucleated and the retinas were excised for proteomic analysis. The proteins were digested with trypsin and fractionated using a pH fractionation kit. The peptides were labeled with a tandem mass tag TMT10plex kit and analyzed with liquid chromatography mass spectrometry. Raw data files were searched against the SwissProt database using MaxQuant software. Protein filtration and statistical analysis by paired t-test were performed in Perseus. GeneCodis3 was used for bioinformatic analysis.
Results :
After filtering, 3718 proteins were identified in the retinas. In retinas treated with intravitreal dexamethasone implants 40 proteins were significantly upregulated (p < 0.05) and 54 proteins were significantly downregulated (p < 0.05). Ozurdex increased the content of proteins involved in mRNA processing, RNA splicing and ATP binding. Mitochondrial proteins were upregulated following Ozurdex intervention. Ozurdex treatment resulted in a downregulation of proteins that were components of the cytosol, plasma membrane and the nucleus. Downregulated biological processes included growth factor binding, integrin binding and endothelial development. Downregulated KEGG pathways included cytokine-cytokine receptor interaction and cell adhesion.
Conclusions :
The data obtained provided new insights into large-scale protein changes resulting from Ozurdex treatment in an experimental model of BRVO. The data indicated that Ozurdex exerts its beneficial effect on the retina by inhibiting growth factor binding, cytokine signaling, integrin signaling and cell adhesion.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.