Multi-Functional OCT Enables Longitudinal Study of Retinal Changes in a VLDLR Knockout Mouse Model

Abstract

We present a multi-functional optical coherence tomography (OCT) imaging approach to study retinal changes in the very-low-density-lipoprotein-receptor (VLDLR) knockout mouse model with a threefold contrast. In the retinas of VLDLR knockout mice spontaneous retinal-chorodoidal neovascularizations form, having an appearance similar to choroidal and retinal neovascularizations (CNV and RNV) in neovascular age-related macular degeneration (AMD) or retinal angiomatous proliferation (RAP). For this longitudinal study, the mice were imaged every 4 to 6 weeks starting with an age of 4 weeks and following up to the age of 11 months. Significant retinal changes were identified by the multi-functional imaging approach offering a threefold contrast: reflectivity, polarization sensitivity (PS) and motion contrast based OCT angiography (OCTA). By use of this intrinsic contrast, the long-term development of neovascularizations was studied and associated processes, such as the migration of melanin pigments or retinal-choroidal anastomosis, were assessed in vivo. Furthermore, the in vivo imaging results were validated with histological sections at the endpoint of the experiment. Multi-functional OCT proves as a powerful tool for longitudinal retinal studies in preclinical research of ophthalmic diseases. Intrinsic contrast offered by the functional extensions of OCT might help to describe regulative processes in genetic animal models and potentially deepen the understanding of the pathogenesis of retinal diseases such as wet AMD.

Polarization sensitive optical coherence tomography – a review [Invited]

“…Several other diseases that affect the macula have been successfully studied by PS-OCT like diabetic retinopathy [129], central serous chorioretinopathy [130], telangiectasia [131], or hereditary diseases like albinism [132] and Stargardt's disease [133]. Moreover, related studies in animal models have been performed [116,134,135]. A detailed description of these results is, however, beyond the scope of this paper.…”

In Vivo Characterization of Spontaneous Retinal Neovascularization in the Mouse Eye by Multifunctional Optical Coherence Tomography

“…[36][37][38] Our group adapted PS-OCT for preclinical imaging of the rodent eye 39,40 and recently extended the method to a multifunctional OCT retinal imaging approach. 41,42 In our past study of the VLDLR knockout mouse model, we introduced a multifunctional OCT approach enabling a description of longterm retinal changes occurring between 1 and 11 months of age. 41 One limitation of that study was the rather late baseline measurement only after neovascularizations, which in the mutant mice usually form between postnatal day (P)14 and P21 12 and had already been well developed.…”

“…In this work we utilized a multifunctional OCT imaging system that was described in detail by Fialová et al 43 and has been recently used to image mouse 41 and rat models 42,44 of ophthalmic diseases. In short, the system is based on a SD, PS-OCT unit enabling high-speed retinal imaging at 83-kHz Ascan rate with an axial resolution of 3.8 lm in retinal tissue.…”

Polarization Sensitive Optical Coherence Tomography: A Review of Technology and Applications

“…Further, PS-OCT has been used for qualitative imaging mostly; the exploitation of quantitative measurements however bears great potential for diagnostics and other applications, as will be demonstrated in the next sections. PS-OCT was also combined with other functional OCT extensions such as Doppler OCT or OCT angiography [30,68,80,[103][104][105]. Such combinations may not only improve the contrast for vascular tissue components but also provide additional, complementary insight into disease patterns [30,103,105,106].…”

“…PS-OCT was also combined with other functional OCT extensions such as Doppler OCT or OCT angiography [30,68,80,[103][104][105]. Such combinations may not only improve the contrast for vascular tissue components but also provide additional, complementary insight into disease patterns [30,103,105,106]. In order to perform PS-OCT beneath the body surface, endoscopic and needle-based PS-OCT was developed [28,29,[107][108][109][110][111][112].…”