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Allison Ning, Jing Cui, Eleanor To, Karen Hsiao Ashe, Joanne Matsubara; Amyloid-β Deposits Lead to Retinal Degeneration in a Mouse Model of Alzheimer Disease. Invest. Ophthalmol. Vis. Sci. 2008;49(11):5136-5143. doi: 10.1167/iovs.08-1849.
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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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