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

Gupta, VK; Chitranshi, N; Gupta, VB; Golzan, M; Dheer, Y; Wall, RV; Georgevsky, D; King, AE; Vickers, JC; Chung, R; Graham, S

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

Gupta, VK Chitranshi, N Gupta, VB Golzan, M

Dheer, Y Wall, RV Georgevsky, D King, AE Vickers, JC Chung, R Graham, S

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Publication Type:: Journal Article
Citation:: Neuroscience Letters, 2016, 623 pp. 52 - 56
Issue Date:: 2016-06-03

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Field	Value	Language
dc.contributor.author	Gupta, VK	en_US
dc.contributor.author	Chitranshi, N	en_US
dc.contributor.author	Gupta, VB	en_US
dc.contributor.author	Golzan, M https://orcid.org/0000-0002-4479-3917	en_US
dc.contributor.author	Dheer, Y	en_US
dc.contributor.author	Wall, RV	en_US
dc.contributor.author	Georgevsky, D	en_US
dc.contributor.author	King, AE	en_US
dc.contributor.author	Vickers, JC	en_US
dc.contributor.author	Chung, R	en_US
dc.contributor.author	Graham, S	en_US
dc.date.available	2016-04-26	en_US
dc.date.issued	2016-06-03	en_US
dc.identifier.citation	Neuroscience Letters, 2016, 623 pp. 52 - 56	en_US
dc.identifier.issn	0304-3940	en_US
dc.identifier.uri	http://hdl.handle.net/10453/123694
dc.description.abstract	© 2016 Elsevier Ireland Ltd. 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.	en_US
dc.relation	http://purl.org/au-research/grants/nhmrc/APP1105930
dc.relation.ispartof	Neuroscience Letters	en_US
dc.relation.isbasedon	10.1016/j.neulet.2016.04.059	en_US
dc.subject.mesh	Optic Nerve	en_US
dc.subject.mesh	Retina	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice, Transgenic	en_US
dc.subject.mesh	Alzheimer Disease	en_US
dc.subject.mesh	Amyloid	en_US
dc.subject.mesh	Amyloid beta-Protein Precursor	en_US
dc.subject.mesh	Intraocular Pressure	en_US
dc.subject.mesh	Dark Adaptation	en_US
dc.subject.mesh	Presenilin-1	en_US
dc.title	Amyloid β accumulation and inner retinal degenerative changes in Alzheimer's disease transgenic mouse	en_US
dc.type	Journal Article
utslib.citation.volume	623	en_US
utslib.for	060105 Cell Neurochemistry	en_US
utslib.for	1109 Neurosciences	en_US
utslib.for	1701 Psychology	en_US
utslib.for	1702 Cognitive Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Graduate School of Health
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	closed_access
pubs.publication-status	Published	en_US
pubs.volume	623	en_US

Abstract:

© 2016 Elsevier Ireland Ltd. 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.

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http://hdl.handle.net/10453/123694