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Anne F Alex, Manuel Ehling, Ralf H. Adams, Nicole Eter; Notch activation controls vascular permeability in laser-induced choroidal neovascularization. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3392.
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To investigate the effect of Notch activation on choroidal neovascularization (CNV) and vascular permeability in a mouse model of laser-induced CNV. Notch is a known mediator in blood vessel maturation and differentiation. Its effect on the mature vessel pattern and pathological neovascularization in the adult eye has not been analyzed.
R26-NICDiΔEC mice were treated with tamoxifen from day 28 to 33 and endothelial cell specific Notch intracellular domain (NICD) overexpression induced via Cre-lox-system. At the age of eight weeks, mice were lasered to rupture retinal piment epithelium (RPE) and Bruchs membrane and to induce CNV. Fluorescence angiography (FA) and immunhistochemical and gene expression (qPCR) analysis for pericytes, cell contacts (VE-Cadherin, ZO-1, Claudin-5) and vascular permeability markers (plasmalemmal vesicle-associated protein (plvap), Glut-1) were performed seven days after laser treatment.
Fluorescence angiography showed reduced hyperfluorescence and reduced leakage after fluorescein injection in Notch activation. Immunhistochemical analysis showed increased ZO-1 expression, reduced plvap expression and an increase of Glut-1 in NICD activation in the area of the laser spot, which indicates a stronger integraty of the outer blood retinal barrier. qPCR analysis showed no difference in Claudin-5 expression, but also a reduction in plvap expression. Pericyte analysis showed no differences in immunhstochemistry.<br />
We were able to show an influence of Notch activation on vascular permeability in a pathologic neovascularization model due to altered cell contact expression and probably to reduced endothelial fenestration in preexisting and neovascular vessels. This might be a first approach to explain poor responder to anti-VEGF therapy in age-related macular degeneration or diabetic retinopathy.
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