Amyloid-beta deposits lead to retinal degeneration in a mouse model of Alzheimer disease.
OBJECTIVE
To compare the temporal and spatial expression patterns of amyloid precursor protein (APP), amyloid-beta 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-beta, 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-beta 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-beta. 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-beta was observed in the choriocapillaris of the older animals.


CONCLUSIONS
Amyloid-beta deposits accumulate with age in the retina of a transgenic mouse model of AD. The amyloid-beta loads are accompanied by increased immunoreactivity for MCP-1, F4/80, and TUNEL-positive profiles in the RGC layer. The results suggest that amyloid-beta causes neurodegeneration in the retina of the doubly mutant transgenic mouse model of AD.
Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, BC, Canada.
Allison
A
Ning
Jing
J
Cui
Eleanor
E
To
Karen Hsiao
KH
Ashe
Joanne
J
Matsubara
D000544:Alzheimer Disease / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D017209:Apoptosis; D015415:Biomarkers; D018932:Chemokine CCL2 / Q000378:metabolism; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008562:Membrane Glycoproteins; D051379:Mice; D008822:Mice, Transgenic; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D012162:Retinal Degeneration / Q000209:etiology / Q000378:metabolism* / Q000473:pathology
D016229:Amyloid beta-Peptides; D000943:Antigens, Differentiation; D015415:Biomarkers; D018932:Chemokine CCL2; D008562:Membrane Glycoproteins; C036763:monocyte-macrophage differentiation antigen