Research articleOCT angiography in the mouse: A novel evaluation method for vascular pathologies of the mouse retina
Introduction
Animal models, among them the mouse, are important for understanding the pathogenesis of retinal and choroidal diseases, including ocular angiogenesis (Aguilar et al., 2008, Montezuma et al., 2009, Grossniklaus et al., 2010).
An important and widely used model is laser-induced choroidal neovascularization (CNV), in which the pathogenesis of wet, age-related macular degeneration (AMD) has been studied and preclinical evaluation of most of the therapeutical approaches to treat this condition has been carried out (Hou et al., 2011, Montezuma et al., 2009, Semkova et al., 2006). For this purpose, ex vivo evaluation of CNV, retinal non-perfusion area or neovascular lesions is performed by histology, immunohistochemistry of retinal or choroidal flat mounts or histological sections. However, these methods do not allow long-term evaluation and monitoring of the same animal at different time points.
In vivo imaging modalities such as fluorescein angiography (FA), spectral-domain optical coherence tomography (SD-OCT) or wide-field laser ophthalmoscopy have been described for the long-term, in vivo characterization and quantification of CNV or other neovascular lesions (Hoerster et al., 2012, Liu et al., 2013, Nakao et al., 2013).
Recently, a new non-invasive imaging technique, OCT angiography, has been developed, by which chorioretinal vascular lesions, neovascularizations and other retinal vascular pathologies can be visualized without the need to apply intravenously injected fluorescent dyes (Ishibazawa et al., 2015, Jia et al., 2012, Jia et al., 2014, Quaranta-El Maftouhi et al., 2015). In addition, OCT angiography enables visualization of blood flow in normal and pathologic vascularization in the different retinal layers. This could help to improve our understanding of retinal neovascular pathologies. While human OCT angiography has attracted increasing interest in clinical practice over the last two years, the method has not yet been evaluated in mice.
In this study, we report for the first time the application of OCT angiography in mice and the usefulness of this novel technique for the imaging of neovascular vessels in the laser-induced CNV mouse model.
Section snippets
Mice
In the present study, we used 10 normal wild-type (WT) C57BL/6J mice aged from 18 to 25 weeks (Charles River, Sulzfeld, Germany). Mice were maintained in our facility on a 12-h day/night cycle, with free access to food and water. Principles of laboratory animal care (NIH publication no. 85-23) were followed. All procedures were performed in accordance with the Declaration of Helsinki. The local ethics committee ‘Landesamt für Natur, Umwelt und Verbraucherschutz Nordrhein-Westfalen (LANUV)’
OCT angiography images in the mouse
For optimized imaging, we used a 20 diopter lens attached to the device by a custom-made holding system (Fig. 1). A platform for the mouse was added to minimize motion artifacts (Fig. 1). The focus in RTVue XR Avanti had to be adjusted manually.
Using the optimized method developed by our group, OCT angiography imaging could be performed routinely. We are now able to visualize the optic disc, retinal vessels in the superficial, deep and the choroid capillary layers in images of a quality
Discussion
Different in vivo imaging methods, allowing long-term observation of the mouse retina, have been developed and introduced in recent years (Montezuma et al., 2009, Liu et al., 2013, Nakao et al., 2013). OCT angiography and the analysis of various diseases of the human retina using OCT angiography have attracted increasing interest over the last few years. It has been described in AMD (Jia et al., 2014), diabetic retinopathy (Ishibazawa et al., 2015), and chronic central serous chorioretinopathy (
Acknowledgments
Funding was provided by the Interdisciplinary Centre for Clinicial Research (IZKF) Münster, “Project Pap2/015/12”. The IZKF has no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
References (21)
- et al.
Ocular models of angiogenesis
Methods Enzymol.
(2008) - et al.
Animal models of choroidal and retinal neovascularization
Prog. Retin Eye Res.
(2010 Nov) - et al.
Quantitative optical coherence tomography angiography of choroidal neovascularization in age-related macular degeneration
Ophthalmology
(2014 Jul) - et al.
Optical coherence tomography angiography of shallow irregular pigment epithelial detachments in pachychoroid spectrum disease
Am. J. Ophthalmol.
(2015 Dec) - et al.
In-vivo and ex-vivo characterization of laser-induced choroidal neovascularization variability in mice
Graefes Arch. Clin. Exp. Ophthalmol.
(2012 Nov) - et al.
Bone marrow-derived cells in neovascular age-related macular degeneration: contribution and potential application
Ophthalmic Res.
(2011) - et al.
Optical coherence tomography angiography in diabetic retinopathy: a prospective pilot study
Am. J. Ophthalmol.
(2015 Jul) - et al.
Quantitative OCT angiography of optic nerve head blood flow
Biomed. Opt. Express
(2012 Dec 1) - et al.
Optical coherence tomography angiography of type 1 neovascularization in age-related macular degeneration
Am. J. Ophthalmol.
(2015 Oct) - et al.
Mapping the 3D connectivity of the rat inner retinal vascular network using OCT angiography
Invest Ophthalmol. Vis. Sci.
(2015 Sep 1)
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These authors contributed equally to this study.