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Laura Emptage, Jennifer J Hunter, Marsha L Kisilak, Melissa L Brooks, Jennifer M Strazzeri, William S Fischer, Louis DiVincenti, Joseph Araujo, Chongzhao Ran, Melanie C W Campbell; Retinal amyloid stained with CRANAD-28 is visible in vivo with fluorescence imaging but not OCT in a canine model of Alzheimer’s disease. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2218.
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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) in humans. As in humans, amyloid beta (Aβ) brain load inversely correlates with cognitive function and dog Aβ has an identical amino acid sequence to human. Here, using a fluorescent marker, we assess whether amyloid deposits in the retina are visible in vivo in fluorescence or OCT imaging with a clinical instrument.
Dogs were categorized by a battery of non-verbal cognitive function tests. Two cognitively impaired dogs and 2 cognitively normal dogs were imaged with a Heidelberg HRA (confocal scanning laser ophthalmoscope with Spectralis spectral domain OCT). They were first imaged in blue laser auto-fluorescence, then given IV injections of CRANAD-28, a marker for amyloid, with a fluorescence excitation peak at 498nm and an emission peak at 578nm. Additional images were taken 5 minutes post injection. Areas newly positive for fluorescence post injection were scanned with OCT and overlaid on the HRA images.
There were punctate auto-fluorescent features in all retinas prior to injection, primarily around the optic nerve head and blood vessels. Post-injection, there were additional fluorescent spots which were not coincident with the auto-fluorescent features. Consistent with our previous ex vivo observations, deposits were present in both the cognitively impaired and cognitively normal animals. Focusing the instrument in the anterior retina produced the best focused fluorescent spots. Thus CRANAD 28 crossed the blood retinal barrier and labelled amyloid deposits in the in vivo retina. OCT B-scans overlaid on the flourescence images were examined but no visible changes were observed at the CRANAD-28 labeled spots.
It has been reported that some other fluorescent amyloid markers do not cross the blood brain barrier in dogs. CRANAD-28, previously developed as a two-photon dye in rodents, crosses the blood retinal barrier and is potentially useful for fluorescence imaging of amyloid deposits in both the brains and the retinas of animal models of AD. These retinal deposits can be imaged in vivo using the auto-fluorescence mode of a clinical instrument. Fluorescent amyloid deposits in the retina do not produce contrast in OCT images, taken with a clinical instrument.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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