Exploration of structural optic nerve changes in mouse models of retinal and neuronal degeneration with optical coherence tomography

Abstract Purpose The optic nerve head (ONH) is a central feature of the retina, affected in many human ocular pathologies, yet it has remained underexplored in most mouse models of disease. We hypothesize that the analysis of the ONH can yield valuable insight into the phenotype of retinal diseases and that pathological changes can be detected using state-of-the-art optical coherence tomography (OCT). Methods Four mouse models – the 5xFAD, PS19 and APP/PS1 models of Alzheimer’s disease (AD) as well as the SOD1 knockout mouse model – were imaged using a polarization-sensitive OCT system to investigate potential disease related changes of the ONH. 5xFAD and SOD1 animals were investigated longitudinally to study disease progression. Additionally, aging effects in wild type mice were studied. Results Two different analysis methods for the segmentation of the ONH were implemented and evaluated. Longitudinal changes to the ONH in 5xFAD animals were observed, specifically an increase of ONH volume from 3 to 5 months of age followed by a strong decrease until 9 months of age. Significant differences between transgenic (tg) and non-transgenic (ntg) animals, as well as sex dependent distinctions were found. Also, for the APP/PS1 model disease related differences between ntg and tg APP/PS1 were significant. Conclusions We demonstrated a simple segmentation of the ONH structure based on OCT intensity images and show its potential as a preclinical biomarker in amyloid mouse models of AD.