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Laura Emptage, Melanie C W Campbell, Rachel Redekop, Erik Mason, Monika Kitor, Michael Hamel; Comparison of amyloid deposits in retinas of cognitively impaired and cognitively normal beagles. Invest. Ophthalmol. Vis. Sci. 2019;60(9):204.
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© ARVO (1962-2015); The Authors (2016-present)
The beagle dog is a naturally occurring model of Alzheimer’s disease (AD). The beagle dog with cognitive impairment exhibits brain pathology and symptoms similar to humans with AD. From our previous work, we found a sensitivity of 100% and specificity of 60% when comparing cognition to Aβ in the beagle retina. Due to the 40% false positives in this previous data set, we choose to compare amyloid deposits from this data in the retina of beagle dogs with and without symptoms of cognitive dysfunction.
This study adhered to the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. Eyes were enucleated from cognitively impaired (CI, n=3) and cognitively normal (CN, n=5) beagle dogs, euthanized for medical reasons unrelated to this study. Formalin fixed retinas were stained with Thioflavin-S and imaged with a fluorescent microscope equipped with a polarimeter for the detection of thioflavin positive amyloid signals. Segmentation masks were created using the polarization images of deposits that also had a positive signal in fluorescence. From the segmentation masks, blob analysis was conducted in Matlab to calculate: deposit area, cluster area, eccentricity, major axis, minor axis, orientation, perimeter. T-tests were run to compare CI deposits (n=28) from and CN deposits (n=66) on the mentioned properties from the retinas examined with polarization as well as age and number of deposits.
Size (Area, cluster area, major axis, minor axis, perimeter), were significantly different (p≤0.05) in deposits between CI dogs and CN dogs. The average area of a CI deposits is 5416 µ2 and the average area of a CN deposits is 3636 µ2. CN dogs had a larger proportion of smaller deposits (69% being under 4000 µ2) than CI subjects (36% being under 4000 µ2). Number of deposits was not significantly different between the two groups (P=0.4920). The age was statically different (p=0.028) between CI (µ= 18.6) and CN (µ= 7.9) dogs.
The similar number of deposits in CI and CN dogs, higher proportion of small deposits in the CN dogs, and younger age of CN subjects, suggests over time amyloid accumulates in existing deposits, making them larger, and less so in new smaller deposits. Therefor proportion of area of deposits and age of dog is likely indicative of disease stage rather than number of deposits in this model.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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