title: Amyloid β accumulation and inner retinal degenerative changes in Alzheimer's disease transgenic mouse.
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.
authors.affiliation: Faculty of Medicine and Health sciences, Macquarie University, Australia. Electronic address: vivek.gupta@mq.edu.au.
authors.forename: Vivek K
authors.initials: VK
authors.lastname: Gupta
authors.affiliation: Faculty of Medicine and Health sciences, Macquarie University, Australia.
authors.forename: Nitin
authors.initials: N
authors.lastname: Chitranshi
authors.affiliation: School of Medical Sciences, Edith Cowan University, Perth, Australia.
authors.forename: Veer B
authors.initials: VB
authors.lastname: Gupta
authors.affiliation: Faculty of Medicine and Health sciences, Macquarie University, Australia.
authors.forename: Mojtaba
authors.initials: M
authors.lastname: Golzan
authors.affiliation: Faculty of Medicine and Health sciences, Macquarie University, Australia.
authors.forename: Yogita
authors.initials: Y
authors.lastname: Dheer
authors.affiliation: Faculty of Medicine and Health sciences, Macquarie University, Australia.
authors.forename: Roshana Vander
authors.initials: RV
authors.lastname: Wall
authors.affiliation: Faculty of Medicine and Health sciences, Macquarie University, Australia.
authors.forename: Dana
authors.initials: D
authors.lastname: Georgevsky
authors.affiliation: Wicking Dementia Research & Education Centre, School of Medicine, University of Tasmania, Australia.
authors.forename: Anna E
authors.initials: AE
authors.lastname: King
authors.affiliation: Wicking Dementia Research & Education Centre, School of Medicine, University of Tasmania, Australia.
authors.forename: James C
authors.initials: JC
authors.lastname: Vickers
authors.affiliation: Faculty of Medicine and Health sciences, Macquarie University, Australia.
authors.forename: Roger
authors.initials: R
authors.lastname: Chung
authors.affiliation: Faculty of Medicine and Health sciences, Macquarie University, Australia; Save Sight Institute, Sydney University, Australia.
authors.forename: Stuart
authors.initials: S
authors.lastname: Graham
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000682:Amyloid / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D003623:Dark Adaptation; D007429:Intraocular Pressure; D008822:Mice, Transgenic; D009900:Optic Nerve / Q000648:ultrastructure; D053764:Presenilin-1 / Q000235:genetics; D012160:Retina / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
chemical_list: D000682:Amyloid; D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1
keywords: Aggregation; Amyloid beta; Electrophysiology recordings; Intraocular pressure; Retina