June 2015
Volume 56, Issue 7
ARVO Annual Meeting Abstract  |   June 2015
Notch activation controls vascular permeability in laser-induced choroidal neovascularization
Author Affiliations & Notes
  • Anne F Alex
    Department of Ophthalmology, University of Muenster Medical Center, Muenster, Germany
  • Manuel Ehling
    VIB3 Vesalius Research Center, Leuven, Belgium
  • Ralf H. Adams
    Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, Muenster, Germany
  • Nicole Eter
    Department of Ophthalmology, University of Muenster Medical Center, Muenster, Germany
  • Footnotes
    Commercial Relationships Anne Alex, Bayer (F), Novartis (F); Manuel Ehling, None; Ralf Adams, None; Nicole Eter, Allergan (C), Bayer (C), Heidelberg Engineering (C), Novartis (C)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 3392. doi:
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    • Get Citation

      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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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: 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.

Methods: 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.

Results: 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 />

Conclusions: 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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