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M. C. W. Campbell, L. J. F. Gowing, Y. Choi, Z. Leonenko; Imaging of Amyloid-Beta Deposits in the Postmortem Retina in Alzheimer’s Disease. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5778.
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The goal of this work is to characterize amyloid-beta deposits in the human retina in Azheimer's disease (AD). Retinal function has been reported to be directly affected by AD and neurotoxic affects of amyloid–beta have been demonstrated in the retina. Amyloid-beta has been found postmortem in human retinas in association with age related macular degeneration and glaucoma in differing locations and in the crystalline lens. There is a single report of amyloid-beta in postmortem human retinas with AD and amyloid-beta deposits have also been found in the optic nerve fibre layer (ONFL) of mouse models of AD. Thus atomic force microscopy (AFM) measurements of the deposits may be possible ex vivo in the human retina in combination with fluorescence microscopy. This would provide nanoscale characterization of amyloid-beta deposits and their location.
Donor eyes were obtained following informed consent under the auspices of the Eye Bank of Canada, Ontario division. Whole mounts without the RPE were prepared of post-mortem retinas within 48 hours of death of one 86 year-old subject with a history of dementia and one 92 year old subject with AD. Both retinas were stained with thioflavin S and examined with fluorescence using a combined AFM/fluorescence microscope from JPK Instruments. In one retina, fluorescently labeled structures and nearby structures were compared to phase and morphological images obtained by AFM. Simultaneous imaging in fluorescence and AFM allowed direct image overlay.
Thioflavin S fluorescence, indicative of amyloid-beta was observed in both retinas, in various layers, including the ONFL and deeper layers. Globular and fibrillar structures were observed. Co-located AFM images confirmed that some of both types of fluorescent structures were located close to the surface of the retina. Phase and morphological differences were observed between these structures and surrounding tissue. AFM gave three dimensional details of the fluorescent structures found near the retinal surface and of the ONFL at nanoscale resolution.
These postmortem retinas with a history of dementia showed evidence of amyloid-beta deposits in fluorescence imaging in the ONFL. AFM combined with fluorescence microscopy will allow us to characterize the location and morphology of these deposits in whole mounted retinas in more detail.
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