title: Investigations into Retinal Pathology in the Early Stages of a Mouse Model of Alzheimer's Disease.
abstract: There is increasing recognition that visual performance is impaired in early stages of Alzheimer's disease (AD); however, no consensus exists as to the mechanisms underlying this visual dysfunction, in particular regarding the timing, nature, and extent of retinal versus cortical pathology. If retinal pathology presents sufficiently early, it offers great potential as a source of novel biomarkers for disease diagnosis. The current project utilized an array of immunochemical and molecular tools to perform a characterization of retinal pathology in the early stages of disease progression using a well-validated mouse model of AD (APPSWE/PS1ΔE9). Analytical endpoints included examination of aberrant amyloid and tau in the retina, quantification of any neuronal degeneration, delineation of cellular stress responses of neurons and particularly glial cells, and investigation of oxidative stress. Brain, eyes, and optic nerves were taken from transgenic and wild-type mice of 3 to 12 months of age and processed for immunohistochemistry, qPCR, or western immunoblotting. The results revealed robust expression of the human APP transgene in the retinas of transgenic mice, but a lack of identifiable retinal pathology during the period when amyloid deposits were dramatically escalating in the brain. We were unable to demonstrate the presence of amyloid plaques, dystrophic neurites, neuronal loss, macro- or micro-gliosis, aberrant cell cycle re-entry, oxidative stress, tau hyperphosphorylation, or upregulations of proinflammatory cytokines or stress signaling molecules in the retina. The overall results do not support the hypothesis that detectable retinal pathology occurs concurrently with escalating amyloid deposition in the brains of APPSWE/PS1ΔE9 mice.
authors.affiliation: Ophthalmic Research Laboratories, Hanson Institute Centre for Neurological Diseases, Adelaide, SA, Australia.|Department of Ophthalmology and Visual Sciences, University of Adelaide, Adelaide, SA, Australia.
authors.forename: Glyn
authors.initials: G
authors.lastname: Chidlow
authors.affiliation: Ophthalmic Research Laboratories, Hanson Institute Centre for Neurological Diseases, Adelaide, SA, Australia.|Department of Ophthalmology and Visual Sciences, University of Adelaide, Adelaide, SA, Australia.
authors.forename: John P M
authors.initials: JP
authors.lastname: Wood
authors.affiliation: School of Medicine, University of Adelaide, Adelaide, SA, Australia.
authors.forename: Jim
authors.initials: J
authors.lastname: Manavis
authors.affiliation: School of Medicine, University of Adelaide, Adelaide, SA, Australia.|SA Pathology, Hanson Institute Centre for Neurological Diseases, Adelaide, SA, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Finnie
authors.affiliation: Ophthalmic Research Laboratories, Hanson Institute Centre for Neurological Diseases, Adelaide, SA, Australia.|Department of Ophthalmology and Visual Sciences, University of Adelaide, Adelaide, SA, Australia.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Casson
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008822:Mice, Transgenic; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009900:Optic Nerve / Q000378:metabolism / Q000473:pathology; D009929:Organ Size; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012160:Retina / Q000378:metabolism / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016875:tau Proteins / Q000378:metabolism
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; C558298:Mapt protein, mouse; C508853:PSEN1 protein, human; D053764:Presenilin-1; D016875:tau Proteins
keywords: Alzheimer’s disease; early biomarker; microglia; müller cell; retina; retinal ganglion cell