Abstract
The mouse model of oxygen-induced retinopathy (OIR) is a well established model to study retinal angiogenesis. It has been used extensively to investigate the mechanisms behind pathologic vessel formation in the eye and has helped to lay the foundations for clinical trials. For example, the current use of intravitreal anti-VEGF agents for neovascular eye disease has been significantly influenced by findings in the OIR mouse model. Originally described in 1994, many detailed reports on the OIR mouse model exist and some examples are given in this chapter. The focus of this chapter, however, lies on a novel tool to reliably quantify retinal neovascularization (NV) in the OIR mouse model. Reliable and standardized NV measurements allow better comparabiltiy between labs and will help to further establish the OIR mouse model as a standard tool in retinal angiogenesis research.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Gyllensten LJ, Hellstrom BE (1954) Experimental approach to the pathogenesis of retrolental fibroplasia. I. Changes of the eye induced by exposure of newborn mice to concentrated oxygen. Acta Paediatr Suppl 43(100):131–148
Dorrell MI, Friedlander M (2006) Mechanisms of endothelial cell guidance and vascular patterning in the developing mouse retina. Prog Retin Eye Res 25(3):277–295
Aguilar E et al (2008) Chapter 6. Ocular models of angiogenesis. Methods Enzymol 444:115–158
Otani A et al (2002) A fragment of human TrpRS as a potent antagonist of ocular angiogenesis. Proc Natl Acad Sci USA 99(1):178–183
D’Amato R, Wesolowski E, Smith LE (1993) Microscopic visualization of the retina by angiography with high-molecular-weight fluorescein-labeled dextrans in the mouse. Microvasc Res 46(2):135–142
Ritter MR et al (2005) Three-dimensional in vivo imaging of the mouse intraocular vasculature during development and disease. Invest Ophthalmol Vis Sci 46(9):3021–3026
Stone J et al (1995) Development of retinal vasculature is mediated by hypoxia-induced vascular endothelial growth factor (VEGF) expression by neuroglia. J Neurosci 15(7 Pt 1):4738–4747
Gerhardt H et al (2003) VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. J Cell Biol 161(6):1163–1177
Benedito R et al (2009) The notch ligands Dll4 and Jagged1 have opposing effects on angiogenesis. Cell 137(6):1124–1135
Hellstrom M et al (2007) Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis. Nature 445(7129):776–780
Lobov IB et al (2007) Delta-like ligand 4 (Dll4) is induced by VEGF as a negative regulator of angiogenic sprouting. Proc Natl Acad Sci USA 104(9):3219–3224
Xu Q et al (2004) Vascular development in the retina and inner ear: control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair. Cell 116(6):883–895
Ye X et al (2009) Norrin, frizzled-4, and Lrp5 signaling in endothelial cells controls a genetic program for retinal vascularization. Cell 139(2):285–298
Stefater JA 3rd et al (2011) Regulation of angiogenesis by a non-canonical Wnt-Flt1 pathway in myeloid cells. Nature 474(7352):511–515
Lobov IB et al (2005) WNT7b mediates macrophage-induced programmed cell death in patterning of the vasculature. Nature 437(7057):417–421
Smith LE et al (1994) Oxygen-induced retinopathy in the mouse. Invest Ophthalmol Vis Sci 35(1):101–111
Pierce EA et al (1995) Vascular endothelial growth factor/vascular permeability factor expression in a mouse model of retinal neovascularization. Proc Natl Acad Sci USA 92(3):905–909
Smith LE et al (1999) Regulation of vascular endothelial growth factor-dependent retinal neovascularization by insulin-like growth factor-1 receptor. Nat Med 5(12):1390–1395
Aiello LP et al (1995) Suppression of retinal neovascularization in vivo by inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-receptor chimeric proteins. Proc Natl Acad Sci USA 92(23):10457–10461
Rota R et al (2004) Marked inhibition of retinal neovascularization in rats following soluble-flt-1 gene transfer. J Gene Med 6(9):992–1002
Bainbridge JW et al (2002) Inhibition of retinal neovascularisation by gene transfer of soluble VEGF receptor sFlt-1. Gene Ther 9(5):320–326
Connor KM et al (2009) Quantification of oxygen-induced retinopathy in the mouse: a model of vessel loss, vessel regrowth and pathological angiogenesis. Nat Protoc 4(11):1565–1573
Stahl A et al (2009) Computer-aided quantification of retinal neovascularization. Angiogenesis 12(3):297–301
Higgins RD et al (1999) Diltiazem reduces retinal neovascularization in a mouse model of oxygen induced retinopathy. Curr Eye Res 18(1):20–27
Lange C et al (2007) Intravitreal injection of the heparin analog 5-amino-2-naphthalenesulfonate reduces retinal neovascularization in mice. Exp Eye Res 85(3):323–327
Chen J et al (2008) Erythropoietin deficiency decreases vascular stability in mice. J Clin Invest 118(2):526–533
Connor KM et al (2007) Increased dietary intake of omega-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis. Nat Med 13(7):868–873
Ritter MR et al (2006) Myeloid progenitors differentiate into microglia and promote vascular repair in a model of ischemic retinopathy. J Clin Invest 116(12):3266–3276
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media Dordrecht
About this chapter
Cite this chapter
Stahl, A., Chen, J., Joyal, JS., Smith, L.E.H. (2012). The Mouse Model of Oxygen-Induced Retinopathy (OIR). In: Zudaire, E., Cuttitta, F. (eds) The Textbook of Angiogenesis and Lymphangiogenesis: Methods and Applications. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4581-0_11
Download citation
DOI: https://doi.org/10.1007/978-94-007-4581-0_11
Published:
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-007-4580-3
Online ISBN: 978-94-007-4581-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)