Retinal structure and function changes in the TgF344-AD rat model of Alzheimer’s disease

Abstract

Purpose : Alzheimer’s disease is a neurodegenerative disease where there is an accumulation of amyloid-beta plaques and neurofibrillary tangles of Tau protein within the brain. In this study, we aimed to determine if retinal changes preceded and are associated with cognitive decline in the TgF-344-AD transgenic rat model of Alzheimer’s disease.

Methods : In TgF344-AD transgenic rats (n=7-12) and wild type littermate controls (Fischer 344 background, n=5-12), the following parameters were assessed at 3, 6, and/or 15 months: retinal function (electroretinography, ERG), retinal structure (spectral-domain optical coherence tomography, SD-OCT), and spatial memory (Barnes maze). At 16 months, rats were euthanized to acquire the brains and retinas, which were analyzed for amyloid precursor protein (APP) via western blot.

Results : Significant delays in ERG oscillatory potential (OP) implicit times were observed in TgF344-AD rats by 6 months (p<0.001), and significant delays in both OP and positive scotopic threshold response (STR) were observed at 15 months (p<0.01 for both). TgF344-AD rats also showed significant thinning of the inner and outer segments at 6 months (p<0.01), as measured by SD-OCT. Significant cognitive deficits (latency) were observed in TgF344-AD rats at 15 months of age (p<0.01). The retinas and brains of TgF-344 AD rats showed an increase in levels of APP.

Conclusions : Retinal function and structure changes were exhibited by the TgF344-AD transgenic rat model prior to an age-related cognitive decline. These results suggest that non-invasive retinal biomarkers may be useful in the diagnosis and staging of Alzheimer’s disease. Future research will investigate retinal astrocyte number and morphology.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.