Spontaneous CNV in a novel mutant mouse is associated with early VEGF-A-driven angiogenesis and late-stage focal edema, neural cell loss, and dysfunction

Norihiro Nagai, Pete Lundh von Leithner, Kanako Izumi-Nagai, Brett Hosking, Bo Chang, Ron Hurd, Peter Adamson, Anthony P. Adamis, Richard H. Foxton, Yin Shan Ng, David T. Shima

研究成果: Article

29 引用 (Scopus)

抜粋

Purpose. Characterization of a mouse model of spontaneous choroidal neovascularization (sCNV) and its effect on retinal architecture and function. Methods. The sCNV mouse phenotype was characterized by using fundus photography, fluorescein angiography, confocal scanning laser ophthalmoscopy (SLO), optical coherence tomography (OCT), ERG, immunostaining, biochemistry, and electron microscopy. A role for VEGF-A signaling in sCNV was investigated by using neutralizing antibodies and a role for macrophages explored by cell-depletion studies. Results. The sCNV starts between postnatal day 10 and 15 (P10-P15), increasing in number and severity causing RPE disruption and dysfunction. Various morphological methods confirmed the choroidal origin and subretinal position of the angiogenic vessels. At approximately P25, vessels were present in the outer retina with instances of anastomosis of some sCNV lesions with the retinal vasculature. The number of CNV lesions was significantly decreased by systemic blockade of the VEGF-A pathway. Choroidal neovascularization size also was significantly modulated by reducing the number of lesion-associated macrophages. Later stages of sCNV were associated with edema, neuronal loss, and dysfunction. Conclusions. The sCNV mouse is a new model for the study of both early and late events associated with choroidal neovascularization. Pharmacological reduction in sCNV with VEGFA antagonists and an anti-inflammatory strategy suggests the model may be useful for investigating novel targets for treating human ocular neovascular disease.

元の言語English
ページ(範囲)3709-3719
ページ数11
ジャーナルInvestigative Ophthalmology and Visual Science
55
発行部数6
DOI
出版物ステータスPublished - 2014 5 20

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

フィンガープリント Spontaneous CNV in a novel mutant mouse is associated with early VEGF-A-driven angiogenesis and late-stage focal edema, neural cell loss, and dysfunction' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

  • これを引用

    Nagai, N., von Leithner, P. L., Izumi-Nagai, K., Hosking, B., Chang, B., Hurd, R., Adamson, P., Adamis, A. P., Foxton, R. H., Ng, Y. S., & Shima, D. T. (2014). Spontaneous CNV in a novel mutant mouse is associated with early VEGF-A-driven angiogenesis and late-stage focal edema, neural cell loss, and dysfunction. Investigative Ophthalmology and Visual Science, 55(6), 3709-3719. https://doi.org/10.1167/iovs.14-13989