September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Retinal amyloid stained with CRANAD-28 is visible in vivo with fluorescence imaging but not OCT in a canine model of Alzheimer’s disease
Author Affiliations & Notes
  • Laura Emptage
    Physics and Astronomy, University of Waterloo, Waterloo, Ontario, Canada
  • Jennifer J Hunter
    Flaum Eye Institute, Center for Visual Science and Biomedical Engineering, University of Rochester, Rochester, New York, United States
  • Marsha L Kisilak
    Physics and Astronomy, University of Waterloo, Waterloo, Ontario, Canada
  • Melissa L Brooks
    Vivicore Inc, Toronto, Ontario, Canada
  • Jennifer M Strazzeri
    Flaum Eye Institute, University of Rochester, Rochester, New York, United States
  • William S Fischer
    Flaum Eye Institute, University of Rochester, Rochester, New York, United States
  • Louis DiVincenti
    Department of Comparative Medicine, Univeristy of Rochester School of Medicine & Dentistry, Rochester, New York, United States
  • Joseph Araujo
    InterVivo Solutions, Toronto, Ontario, Canada
  • Chongzhao Ran
    Molecular Imaging Laboratory, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States
  • Melanie C W Campbell
    Physics and Astronomy, University of Waterloo, Waterloo, Ontario, Canada
    School of Optometry and Vision Science, University of Waterloo, Waterloo, Ontario, Canada
  • Footnotes
    Commercial Relationships   Laura Emptage, None; Jennifer Hunter, Polgenix Inc. (F), University of Rochester (P); Marsha Kisilak, None; Melissa Brooks, Vivocore (E); Jennifer Strazzeri, None; William Fischer, None; Louis DiVincenti, None; Joseph Araujo, InterVivo Solutions (E); Chongzhao Ran, Massachusetts General Hospital (P); Melanie Campbell, InterVivo Solutions (F), University of Waterloo (P)
  • Footnotes
    Support  This research was supported by the Collaborative Health Research Program with NSERC Canada grant number 052549 and CIHR Canada grant number 052509, by an Unrestricted Grant to the University of Rochester Department of Ophthalmology from Research to Prevent Blindness, New York, New York and by the National Eye Institute of the National Institutes of Health under Award No. P30 EY001319. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 2218. doi:
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    • Get Citation

      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)

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Abstract

Purpose : 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.

Methods : 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.

Results : 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.

Conclusions : 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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