Retinal analysis of a mouse model of Alzheimer’s disease with multicontrast optical coherence tomography

Abstract

Recent Alzheimer's disease (AD) patient studies have focused on retinal analysis, as the retina is the only part of the central nervous system which can be imaged non-invasively by optical methods. However as this is a relatively new approach, the occurrence and role of pathological features such as retinal layer thinning, extracellular amyloid beta (A$\beta$) accumulation and vascular changes is still debated. Animal models of AD are therefore often used in attempts to understand the disease. In this work, both eyes of 24 APP/PS1 transgenic mice (age: 45-104 weeks) and 15 age-matched wildtype littermates were imaged by a custom-built multi-contrast optical coherence tomography (OCT) system. The system provided a combination of standard reflectivity data, polarization-sensitive data and OCT angiograms. This tri-fold contrast provided qualitative and quantitative information on retinal layer thickness and structure, presence of hyper-reflective foci, phase retardation abnormalities and retinal vasculature. While abnormal structural properties and phase retardation signals were observed in the retinas, the observations were very similar in transgenic and control mice. At the end of the experiment, retinas and brains were harvested from a subset of the mice (14 transgenic, 7 age-matched control) in order to compare the in vivo results to histological analysis, and to quantify the cortical A$\beta$ plaque load.