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Amyloid β accumulation and inner retinal degenerative changes in Alzheimer's disease transgenic mouse

Citation

Gupta, VK and Chitranshi, N and Gupta, VB and Golzan, M and Dheer, Y and Wall, RV and Georgevsky, D and King, AE and Vickers, JC and Chung, R and Graham, S, Amyloid β accumulation and inner retinal degenerative changes in Alzheimer's disease transgenic mouse, Neuroscience Letters, 623 pp. 52-56. ISSN 0304-3940 (2016) [Refereed Article]

Copyright Statement

© 2016 Elsevier

DOI: doi:10.1016/j.neulet.2016.04.059

Abstract

The APP-PS1ΔE9 mouse model of Alzheimer’s disease (AD) exhibits age dependent amyloid β (Aβ) plaque formation in their central nervous system due to high expression of mutated human APP and PSEN1 transgenes. Here we evaluated Aβ deposition and changes in soluble Aβ accumulation in the retinas of aged APP-PS1 mice using a combination of immunofluorescence, retinal flat mounts and western blotting techniques. Aβ accumulation in the retina has previously been shown to be associated with retinal ganglion cell apoptosis in animal models of glaucoma. This study investigated changes in the inner retinal function and structure in APP-PS1 mice using electrophysiology and histological approaches respectively. We report for the first time a significant decline in scotopic threshold response (STR) amplitudes which represents inner retinal function in transgenic animals compared to the wild type counterparts (p < 0.0001). Thinning of the retina particularly involving inner retinal layers and reduction in axonal density in the optic nerve was also observed. TUNEL staining was performed to examine neuronal apoptosis in the inner retina. Intraocular pressure (IOP) measurements showed that APP-PS1ΔE9 mice had a slightly elevated IOP, but the significance of this finding is not yet known. Together, these results substantiate previous observations and highlight that APP-PS1ΔE9 mice show evidence of molecular, functional and morphological degenerative changes in the inner retina.

Item Details

Item Type:Refereed Article
Keywords:dementia, Alzhiemer's disease, amyloid beta, retina, electrophysiology recordings, intraocular pressure, aggregation
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Cellular Nervous System
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
Author:King, AE (Associate Professor Anna King)
Author:Vickers, JC (Professor James Vickers)
ID Code:110086
Year Published:2016
Web of Science® Times Cited:15
Deposited By:Wicking Dementia Research and Education Centre
Deposited On:2016-07-12
Last Modified:2017-11-06
Downloads:0

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