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Andreas Ebneter, Cavit Agca, Sebastian Wolf, Volker Enzmann, Martin Sebastian Zinkernagel; Characterization of a refined mouse model of retinal vein occlusion. Invest. Ophthalmol. Vis. Sci. 2014;55(13):6179. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal vein occlusion represents a chronic disorder of the inner retina with hypoxia, vascular leakage and neuronal degeneration causing significant morbidity. A reliable retinal vein occlusion model in mice would be a valuable tool for the investigation of specific questions regarding this disease using genetically modified animals. The aim of the current work was to refine and further characterize a model of retinal vein occlusion in mice.
Retinal vein occlusion was induced in BALB/c mice by indirect laser photocoagulation (532 nm) of 1-2 veins one disc diameter from the optic nerve after intravenous tail vein injection of Rose Bengal (25mg/kg), a photo-activator dye to enhance thrombus formation. Color fundus photographs (Optomap), retinal OCT imaging and fluorescein angiography using a 55° optic were performed at baseline, days 3, 7 and 14 after induction of the venous blockage. Mice were killed at various time-points and eyes processed for histology.
Experimental retinal vein occlusion caused significant vascular change in the affected retina with remodeling of capillaries and shunt-vessel formation (Fig. 1). However, significant retinal thickening was not seen during the observational period using OCT imaging in this model with relatively mild laser. Nonetheless, retinal thinning (Fig. 2) was observed in the affected quadrant from day 7 onwards on OCT (p<0.001; one-way ANOVA for repeated measures). Imaging data corresponded well with findings on hematoxylin/eosin sections (Fig. 2).
Similar to the changes in humans suffering from retinal vein occlusion, experimental venous blockage induced shunt-vessel formation. Different intensities of laser application may mimic different severities of disease. However, some facets of human macular disease such as leakage and edema may not be appropriately represented due to structural differences. Further studies are needed to closer characterize this model, but the paradigm seems suitable to gain valuable insight into patho-mechanisms occurring during vascular remodeling after vein occlusion and other aspects of ischemic retinal disease.
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