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Originally published In Press as doi:10.1167/iovs.08-1849 on June 19, 2008
 (Investigative Ophthalmology and Visual Science. 2008;49:5136-5143.)
© 2008 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.08-1849
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Amyloid-β Deposits Lead to Retinal Degeneration in a Mouse Model of Alzheimer Disease

Allison Ning,1 Jing Cui,1 Eleanor To,1 Karen Hsiao Ashe,2 and Joanne Matsubara1

1From the Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, BC, Canada; and the 2Department of Neurology, University of Minnesota, Minneapolis, Minnesota.

PURPOSE. To compare the temporal and spatial expression patterns of amyloid precursor protein (APP), amyloid-β deposits, inflammatory chemokines, and apoptosis in the retina of a mouse model of Alzheimer disease (AD).

METHODS. Retinas of transgenic mice harboring a mutant presenilin (PS1) and a mutant APP gene were processed for TUNEL and immunohistochemistry with antibodies against APP, amyloid-β, monocyte chemotactic protein (MCP)-1, and F4/80. Comparisons were made between age groups and between transgenic and wild-type congeners.

RESULTS. The neuroretina demonstrated age-dependent increases in APP in the ganglion cells (RGCs) and in neurons of the inner nuclear layer (INL). Amyloid-β demonstrated significant age-dependent deposition in the nerve fiber layer (NFL). TUNEL-positive RGC increased in an age-dependent fashion and in transgenic compared with wild-type congeners. Concomitant overexpression of MCP-1 and intense immunoreactivity for F4/80 suggested that RGCs upregulate MCP-1 in response to amyloid-β. Activated microglia proliferated in response to MCP-1. In the outer retina, retinal pigment epithelium (RPE) demonstrated moderate age-dependent APP immunoreactivity, but nearby drusenlike deposits were not present. Amyloid-β was observed in the choriocapillaris of the older animals.

CONCLUSIONS. Amyloid-β deposits accumulate with age in the retina of a transgenic mouse model of AD. The amyloid-β loads are accompanied by increased immunoreactivity for MCP-1, F4/80, and TUNEL-positive profiles in the RGC layer. The results suggest that amyloid-β causes neurodegeneration in the retina of the doubly mutant transgenic mouse model of AD.




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