Amyloid-β Deposits Lead to Retinal Degeneration in a Mouse Model of Alzheimer Disease
Top Cited Papers
- 1 November 2008
- journal article
- research article
- Published by Association for Research in Vision and Ophthalmology (ARVO) in Investigative Ophthalmology & Visual Science
- Vol. 49 (11), 5136-43
- https://doi.org/10.1167/iovs.08-1849
Abstract
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). 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. 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. 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.This publication has 55 references indexed in Scilit:
- Optometric management of patients with Alzheimer's disease.1997
- Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic MiceScience, 1996
- Increased amyloid-β42(43) in brains of mice expressing mutant presenilin 1Nature, 1996
- Retinal pathology in Alzheimer's disease. I. Ganglion cell loss in foveal/parafoveal retinaNeurobiology of Aging, 1996
- Retinal pathology in Alzheimer's disease. II. Regional neuron loss and glial changes in GCLNeurobiology of Aging, 1996
- Retinal nerve fiber layer abnormalities in Alzheimer's diseaseActa Ophthalmologica Scandinavica, 1996
- Brain Parenchymal and Microvascular Amyloid in Alzheimer's DiseaseBrain Pathology, 1996
- Alzheimer-type neuropathology in transgenic mice overexpressing V717F β-amyloid precursor proteinNature, 1995
- Complement activation by beta-amyloid in Alzheimer disease.Proceedings of the National Academy of Sciences of the United States of America, 1992
- Retinal Degeneration in the Macula of Patients with Alzheimer's DiseaseaAnnals of the New York Academy of Sciences, 1991