Impaired inner retinal function and Amyloid β aggregation is demonstrated in a mouse model of Alzheimer's disease

Purpose: Abnormal amyloid precursor protein (APP) expression and amyloid β (Aβ) deposition have been shown to be involved in the development of retinal ganglion cell apoptosis in glaucoma. The APP-PS1 mouse model of Alzheimer’s disease (AD) expresses several fold higher mutated human APP and PSEN1 transgenes compared to the endogenous murine APP. These mice exhibit age dependent Aβ plaque formation in their central nervous system. Here we evaluated Aβ aggregate formation in the retinas of these mice and compared it to WT animals. Intraocular pressure (IOP) in these transgenic animals was also evaluated. The impact of genetic modification and AD like pathology on the inner retinal function was investigated with electrophysiology. Methods: Wild type and age-matched APP-PS1 transgenic littermates (13-16 month) were used to assess the inner retinal and whole retinal physiology using the scotopic threshold response (STR) and scotopic electroretinogram (ERG) respectively (n=20). Intraocular pressure was examined using rebound tonometer and averaged (iCare) (n=20). Retinas were flat-mounted under the microscope and Aβ deposition pattern investigated histologically using Thioflavin-S staining. Results: The genetic manipulation of APP-PS1 genes and resultant AD like pathology manifested itself in the form of a retinal phenotype depicting a preferential loss of STR amplitude in the transgenic animals compared to the wild type counterparts: 47.9 +/- 4.6 uV vs 72.8 +/- 2.3 uV (p<0.0001). Interestingly, the functional changes were also accompanied by slightly elevated IOP in these mice (p