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Laura Emptage, David DeVries, Marsha Kisilak, Melanie C W Campbell, Zoya Leonenko, Howard Dobson, Francisco J. Avila, Theodore Chow, Chris Cookson; Comparison of amyloid beta in the retina of an animal model of Alzheimer’s disease and humans with the disease. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4250.
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© ARVO (1962-2015); The Authors (2016-present)
Beagle dogs suffer from a naturally occurring cognitive dysfunction syndrome, with symptoms and brain pathology similar to Alzheimer’s disease (AD). As in humans, amyloid beta (Aβ) brain load inversely correlates with cognitive function, and appears early. The Aβ has an identical amino acid sequence to human Aβ. Here we assess the beagle dog as a model of retinal pathology in human AD, comparing polarization properties, fluorescence, location and morphology of Aβ deposits.
Dogs were categorized by a battery of non-verbal cognitive function tests. Eyes from 5 cognitively impaired and 5 normal dogs, euthanized for unrelated reasons and eyes from 18 humans with AD and 18 normals were examined. Retinas were fixed in formalin or formaldehyde, stained with either 0.1% thioflavin-S, or 0.01% curcumin, counter stained with DAPI and flat mounted. Retinas were examined with confocal microscopy, atomic force microscopy (AFM), and for fluorescence to characterize the morphology of the Aβ deposits at the nanoscale and their locations. We studied polarization properties of areas with positive fluorescence and in retinas from normals. 16 images were examined for 4 positions each of a generator and analyzer.
Aβ deposits were found close to the retinas’ anterior surface in cognitively impaired dogs and humans with AD and in some dog and human retinas prior to diagnosis of disease. The morphology and positions of deposits in dog are similar to deposits in humans, except that the deposit thickness is often larger in dogs. The polarization properties as given by the Mueller matrix are also similar. In dog and human retinas, the values of polarization properties; depolarization and retardation of deposits were significantly above the values in the surrounding retina and in control retinas (dog p<0.0002 and human p<0.0005). Diattenuation and polarizance were on average higher in dog deposits than in the surrounding retina; this was true for fewer human deposits.
Overall, polarization properties, fluorescence, location and morphology of Aβ deposits were similar in the diseased beagle dog and human. The few differences were consistent with a more severe pathology in dogs. Thus the beagle dog is a valuable model of retinal pathology in human AD. Polarization imaging could potentially allow a non-invasive in vivo diagnosis and tracking of AD.
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