Polarization properties of amyloid deposits in the retinas of an animal model of Alzheimer’s disease differ in those with and without cognitive impairment

Abstract

Purpose : Beagle dogs suffer from a naturally occurring cognitive dysfunction syndrome, with symptoms and brain pathology similar to Alzheimer’s disease. As in humans, it has been observed that brain amyloid deposits often appear prior to a decline in cognitive function. To determine whether retinal amyloid deposits differ in these populations, we compare their polarization properties in cognitively impaired dogs to those in cognitively normal dogs and to retinas in cognitively normal dogs without deposits.

Methods : Dogs were categorized with a battery of non-verbal cognitive function tests. Retinas from 2 cognitively impaired dogs with deposits and 4 cognitively normal dogs, 2 with and 2 without deposits (Control) were compared. Eyes were enucleated from dogs euthanized for unrelated reasons and the retinas were fixed in formalin or formaldehyde, stained with 0.1% Thioflavin-S and flat mounted. Images were taken using polarized light of amyloid deposits, identified by fluorescence using a transmission microscope fitted with a polarimeter. A spatially resolved Mueller Matrix described the pixel by pixel interaction of the retina with polarized light. 38 polarization properties were calculated from the Mueller matrices and compared across retinas. Properties of areas corresponding to 41 deposits were characterized from each group, and compared to 41 areas in Controls which were matched based on retinal location.

Results : Eleven polarization properties were found to significantly (P<0.05) differentiate the deposits in retinas of cognitively impaired dogs (Pos) vs deposits in cognitively normal dogs (PosCon); deposits in Pos vs areas in cognitively normal dogs without deposits (Con) and PosCon vs Con. These properties fell into 3 categories: diattenuation, retardance and degree of polarization. For these 11 properties, the mean values for PosCon fell between those of the Pos and Con.

Conclusions : Polarization properties of retinal amyloid deposits were related to cognitive function. They changed progressively from dogs that were not cognitively impaired and had no amyloid deposits through those not cognitively impaired but with amyloid deposits to cognitively impaired dogs with deposits. Polarization characteristics of amyloid deposits have the potential to track early development of disease in this animal model of Alzheimer’s disease.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.