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Title 

Dry age-related macular degeneration like pathology in aged 5XFAD mice: ultrastructure and microarray analysis

Authors 

S W ParkS ImH O JunK LeeYoung-Jun ParkJ H KimW J ParkY H Lee

Publisher 

Impact Journals

Issue Date 

2017

Citation 

Oncotarget

Keywords 

Age-related macular degenerationAmyloid βGerotargetMicroarrayRetinal pigment epitheliumTransmission electron microscopy

Abstract 

Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly. The two types of AMD are: dry and wet AMD. While laser-induced choroidal neovascularization has been used extensively in the studies of wet AMD, there is no established mouse model that fully recapitulates the cardinal features of dry AMD. A lack of appropriate mouse model for dry AMD has hampered the translational research on the pathogenesis of the disease and the development of therapeutic agents. We hypothesized that 5XFAD mice, an animal model for the study of Alzheimer's disease, can be used as a mouse model for dry AMD with regard to the amyloid beta (Aβ) related pathology. In this study, the ultrastructure of the retinal pigment epithelium (RPE) of 5XFAD mice was analyzed using transmission electron microscopy. Of importance, the aged 5XFAD mice show ultrastructural changes in the RPE and Bruch's membrane (BM) that are compatible with the cardinal features of human dry AMD, including a loss of apical microvilli and basal infolding of the RPE, increased BM thickness, basal laminar and linear deposits, and accumulation of lipofuscin granules and undigested photoreceptor outer segment-laden phagosomes. In microarray-based analysis, the RPE complex of the aged 5XFAD mice shows differential gene expression profiles consistent with dry AMD in the inflammation response, immune reaction pathway, and decreased retinol metabolism. Taken together, we suggest that aged 5XFAD mice can be used as a mouse model of dry AMD to study Aβ related pathology and develop a new therapeutic approaches

ISSN 

1949-2553

Link 

http://dx.doi.org/10.18632/oncotarget.16967

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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