Retinal hyperspectral imaging in mouse models of Parkinson’s disease and healthy aging

Abstract

Purpose : Hyperspectral imaging is a non-invasive imaging method that has shown promise in Alzheimer’s disease. Parkinson’s disease is another neurodegenerative disease where brain pathobiology such as alpha-synuclein and iron overaccumulation have been implicated in the retina. We tested the hypothesis that hyperspectral imaging was altered in two in vivo mouse models of Parkinson’s disease and examined whether this differed from healthy aging.

Methods : Transgenic mouse models that target alpha-synuclein (A53T; 4, 6, 14 months-old) and iron accumulation (TauKO; 8, 18 months) were compared against wild-type littermates (n=8-18/group). To examine healthy ageing, three cohorts of control mice were assessed, C57blk6J, WT controls from A53T and TauKO mice (3-18 months-old). Hyperspectral imaging was conducted from 320-680nm (Polychrome-V light, cMOS camera). Spectral reflectivity was analysed using a two-way ANOVA with Benjamini correction (Prism, GraphPad). Multivariate analysis was performed to examine the influence of healthy aging, alpha-synuclein, iron and RNFL thickness on hyperspectral imaging (MATLAB R2019a).

Results : Older A53T and TauKO mice (14,18 months-old respectively) show significant interaction effects (p<0.001) with increased reflectivity particularly at shorter wavelengths (<550nm). At younger ages A53T and TauKO mice did not show interaction effects (p>0.05). A different pattern of hyperspectral reflectivity was observed in healthy aging, with a reduction in reflectivity with advancing age (p<0.0001). Multivariate analysis of hyperspectral imaging were significant when plotted against age. Moreover, when alpha-synuclein, iron or retinal nerve fibre layer thickness were added as a cofactor this improved R2 in certain groups.

Conclusions : Two mouse models of PD exhibit an alteration in spectral reflectivity of the retina. The hyperspectral signature exhibited with the PD models is distinct from that observed with normal healthy ageing. There is a suggestion that factors including retinal deposition of alpha-synuclein and and retinal nerve fibre layer thickness may play a role. These findings suggest that hyperspectral imaging may be a promising translation tool in the study of Parkinson’s disease.

This abstract was presented at the 2024 ARVO Imaging in the Eye Conference, held in Seattle, WA, May 4, 2024.

 

Normalised plots highlighting the Parkinson's disease (PD) hyperspectral phenotype is distinct from the healthy aging phenotype