Varaka, M. | bioRxiv Science

bioRxiv2026

Exploration of Structural Optic Nerve Changes in Mouse Models of Retinal and Neuronal Degeneration with Optical Coherence Tomography

PurposeThe 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). MethodsFour mouse models - the 5xFAD, PS19 and APP/PS1 models of Alzheimers 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. ResultsTwo 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. ConclusionsWe 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.

neuroscience↗

bioRxiv2025

Longitudinal investigation of spatial memory and retinal parameters in a 5xFAD model of Alzheimers disease reveals differences dependent on genotype and sex

SignificanceThe retinal phenotype of Alzheimers disease (AD) is poorly understood. The connection between spatial memory and retinal phenotype is poorly investigated. Additionally, the influence of sex on the disease in mouse models is not sufficiently clear and requires further investigation. AimTo investigate the retina and spatial memory of 5xFAD mouse models of AD by measuring retinal and behavioral parameters. ApproachA custom-built optical coherence tomography (OCT) system is used to image the retina of both eyes of 32 transgenic 5xFAD mice and 32 non-transgenic littermates over the course of 6 months (3-9 months of age) to investigate retinal parameters. The Morris Water Maze (MWM) test was performed to examine correlations between the retinal and spatial memory phenotype of the mouse model. ResultsData were acquired in the form of OCT reflectivity images and OCT angiograms as well as video recordings of the MWM test. Layer thickness and vascular density were calculated from the resulting data. Behavioral data was extracted from the videos acquired from the MWM. Total retinal and inner retinal layer thickness increased slightly over the measurement period, while outer retinal layer and retinal nerve fiber layer thickness showed no significant change. The correlation analysis between MWM and layer thickness data revelated a positive correlation between inner nuclear layer thickness and MWM test day parameters. ConclusionsOCT and MWM data revealed sex-based differences in the retinal phenotype of the 5xFAD mouse model, with changes in retinal thickness in different stages of the study and dissimilar correlations between retinal and spatial memory phenotype.

neuroscience↗