Elsevier

Experimental Eye Research

Volume 145, April 2016, Pages 417-423
Experimental Eye Research

Research article
OCT angiography in the mouse: A novel evaluation method for vascular pathologies of the mouse retina

https://doi.org/10.1016/j.exer.2016.02.012Get rights and content

Highlights

  • We demonstrate the application of OCT angiography in the mouse retina.

  • We visualize the normal vascular plexus in the different retinal layers.

  • We visualize pathological vascularization in a mouse model of laser-induced CNV.

Abstract

Purpose

To investigate the application of optical coherence tomography (OCT) angiography in the retinas of healthy mice and to evaluate choroidal neovascularization (CNV) in a mouse model of laser-induced CNV.

Methods

C57BL/6J mice aged 18–25 weeks were examined using the spectral-domain optical coherence tomography device RTVue XR Avanti (Optovue, Inc, Fremont, California, USA). Blood flow in different retinal layers was detected using the split-spectrum amplitude-decorrelation angiography algorithm. Fluorescein angiography (FA) images were obtained using the Heidelberg Spectralis device (Heidelberg, Germany).

Results

Using the RTVue XR Avanti, we were able to obtain high-quality OCT angiography images of normal vasculature in the superficial, deep capillary and choriocapillary layers in laser-treated mice and untreated controls. Whereas no blood flow was detectable in the outer retina of untreated mice, blood flow and hence neovascular vessels were found in laser-treated mice.

Conclusions

OCT angiography can clearly visualize the normal vascular plexus in the different retinal layers in the mouse retina and choroid. With OCT angiography, it is possible to verify the choroidal neovascularization induced by laser treatment. Thus, OCT angiography is a helpful imaging tool for non-invasive, in vivo evaluation of laser-induced CNV in the mouse.

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.

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These authors contributed equally to this study.

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