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.

Autor:	Nagai N; Department of Ocular Biology and Therapeutics, University College London, Institute of Ophthalmology, London, United Kingdom., Lundh von Leithner P; Department of Ocular Biology and Therapeutics, University College London, Institute of Ophthalmology, London, United Kingdom., Izumi-Nagai K; Department of Ocular Biology and Therapeutics, University College London, Institute of Ophthalmology, London, United Kingdom., Hosking B; Department of Ocular Biology and Therapeutics, University College London, Institute of Ophthalmology, London, United Kingdom., Chang B; The Jackson Laboratory, Bar Harbor, Maine, United States., Hurd R; The Jackson Laboratory, Bar Harbor, Maine, United States., Adamson P; GSK Ophthalmology, GlaxoSmithKline, Stevenage, Hertfordshire, United Kingdom., Adamis AP; Genentech, Inc., South San Francisco, California, United States., Foxton RH; Department of Ocular Biology and Therapeutics, University College London, Institute of Ophthalmology, London, United Kingdom., Ng YS; Department of Ocular Biology and Therapeutics, University College London, Institute of Ophthalmology, London, United Kingdom., Shima DT; Department of Ocular Biology and Therapeutics, University College London, Institute of Ophthalmology, London, United Kingdom.
Jazyk:	angličtina
Zdroj:	Investigative ophthalmology & visual science [Invest Ophthalmol Vis Sci] 2014 May 20; Vol. 55 (6), pp. 3709-19. Date of Electronic Publication: 2014 May 20.
DOI:	10.1167/iovs.14-13989
Abstrakt:	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 VEGF-A antagonists and an anti-inflammatory strategy suggests the model may be useful for investigating novel targets for treating human ocular neovascular disease. (Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.)
Databáze:	MEDLINE
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