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M. Paques, M. Simonutti, O. Goupille, O. Genevois, J.-A. Sahel; Chronic Microvascular Remodelling and Blood-Retinal Barrier Rupture Following Branch Retinal Vein Occlusion in Wild-Type Mice. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2692.
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Microvascular remodelling is a major cause of visual loss, which may occur through blood-retinal barrier (BRB) rupture causing macular edema and/or capillary drop-out. There is yet no clinically relevant adult animal model of microvascular remodelling in the retina, a situation which impairs therapeutic developments. We revisited the mouse model of branch retinal vein occlusion (BRVO), assuming that, as in humans, achieving permanent occlusion would potentiate microvascular remodelling.
Adult C57 and balb/c mice (n=60) underwent single BRVO by sodium fluorescein-enhanced argon laser disruption of the venous wall. The ensuing microvascular remodelling was observed by iterative in vivo confocal scanning laser ophtalmoscopy fluorescein angiographies during up to 6 months afterwards. Immunohistochemistry on retinal flat-mounts was performed at day 30 and compared to in vivo fluorescein angiographies.
At day 30, the treated vein was still occluded in 72% of eyes after a single procedure. Upstream of the occlusion site, BRB rupture (23% of eyes), capillary closure (35%) and collateral vessel formation (95%) were observed, at various degrees, alone or in combination. BRB rupture occurred in discrete sites located mainly along collateral vessels. Extension of nonperfused areas was inversely proportional to collateral vessel development. No newvessels developed. There was no strain-related effect. Immunohistochemistry showed that collateral vessel maturation was associated to a shift from capillary to venular phenotype, with increased expression of actin. Retinal areas with evidence of capillary closure on agiographies were histologically devoid of vascular structures.
A procedure for long-term BRVO was established in mice, which leads to chronic microvascular remodelling closely mimicking features of the human disease. To our knowledge, this is the first in vivo demonstration of chronic BRB rupture in wild-type adult rodents. The close spatial relationship between collateral vessel formation and BRB rupture suggest that they share common pathways. Such model may be helpful to understand the mechanisms leading to visual loss and to collateral vessel formation in human RVO, and to screen treatments for macular edema.
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