Investigating Retinal Changes in a Mouse Model of Alzheimer’s Disease using OCT

Abstract

Purpose : To investigate retinal changes in a mouse model of Alzheimer’s disease using optical coherence tomography (OCT). To correlate in-vivo retinal changes with ex-vivo histology of the brain.

Methods : A custom-made OCT system for small animal retinal imaging was utilized to investigate the retinas of APP/PS1 double transgenic mice. Mice with the transgene insertion of APPswe and PSEN1dE9 develop beta-amyloid deposits in the brain between 6 to 7 months of age. The retinas of 10 transgenic APP/PS1 mice and 9 age-matched wildtype (WT) litter mates were imaged between 10 and 21 months of age. Volumetric OCT scans were taken close to the optic nerve head in both eyes covering a field-of-view of 1mm². The total, outer and inner retinal thickness were assessed automatically. All datasets were screened for abnormalities such as hyperreflective foci (HRF) or neovascularizations. In-vivo OCT imaging of the retina was followed by ex-vivo brain histological examination.

Results : Imaging the retinas using OCT revealed abnormalities when compared to healthy retinas. HRF in the outer retina were observed in 10 out of 19 APP/PS1 mice eyes, but also in 8 out of 15 age-matched WT eyes. Furthermore, in three mice (2 APP/PS1, 1 WT), the outer nuclear (ONL) and outer plexiform layer (OPL) showed an abnormal appearance, where the ONL was interrupted by the OPL and the ONL was thinned. Cataract formation and HRF in the vitreous were present at the latest instant at 21 months of age. The quantitative evaluation of the total, inner and outer retinal thickness revealed decreasing trends over time for both groups (APP/PS1 and WT). Age-related thinning tended to be stronger for the group of the APP/PS1 mice; however, the difference was not statistically significant. Although the retina of the transgenic and WT mice appeared rather similar in the structural OCT images, only the brains of the APP/PS1 mice clearly showed dense neuritic Aβ plaque deposition.

Conclusions : In-vivo retinal OCT imaging revealed a similar structural appearance of both the APP/PS1 and the WT group with abnormalities present in both groups. While this preliminary analysis did not reveal statistically significant differences, a more detailed quantitative analysis and retinal histology may provide additional insight. A histological comparison of the brains of the two groups showed a clear difference in phenotype, where the brains of APP/PS1 contained a wealth of plaques.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.