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Imaging multiple phases of neurodegeneration: a novel approach to assessing cell death in vivo

Title: Imaging multiple phases of neurodegeneration: a novel approach to assessing cell death in vivo
Authors: Cordeiro, MF
Guo, L
Coxon, KM
Duggan, J
Nizari, S
Normando, EM
Sensi, SL
Sillito, AM
Fitzke, FW
Salt, TE
Moss, SE
Item Type: Journal Article
Abstract: Nerve cell death is the key event in all neurodegenerative disorders, with apoptosis and necrosis being central to both acute and chronic degenerative processes. However, until now, it has not been possible to study these dynamically and in real time. In this study, we use spectrally distinct, well-recognised fluorescent cell death markers to enable the temporal resolution and quantification of the early and late phases of apoptosis and necrosis of single nerve cells in different disease models. The tracking of single-cell death profiles in the same living eye over hours, days, weeks and months is a significant advancement on currently available techniques. We identified a numerical preponderance of late-phase versus early-phase apoptotic cells in chronic models, reinforcing the commonalities between cellular mechanisms in different disease models. We showed that MK801 effectively inhibited both apoptosis and necrosis, but our findings support the use of our technique to investigate more specific anti-apoptotic and anti-necrotic strategies with well-defined targets, with potentially greater clinical application. The optical properties of the eye provide compelling opportunities for the quantitative monitoring of disease mechanisms and dynamics in experimental neurodegeneration. Our findings also help to directly observe retinal nerve cell death in patients as an adjunct to refining diagnosis, tracking disease status and assessing therapeutic intervention.
Issue Date: 14-Jan-2010
Date of Acceptance: 2-Oct-2009
URI: http://hdl.handle.net/10044/1/63312
DOI: https://dx.doi.org/10.1038/cddis.2009.3
ISSN: 2041-4889
Publisher: Nature Publishing Group
Journal / Book Title: Cell Death and Disease
Volume: 1
Copyright Statement: © 2010 The Author(s). This article is licensed under a Creative Commons Attribution-Noncommercial-No DerivativeWorks 3.0 License. To view a copy of this License, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
Keywords: Science & Technology
Life Sciences & Biomedicine
Cell Biology
neurodegeneration
retinal imaging
apoptosis
necrosis
Alzheimer's disease
glaucoma
RETINAL GANGLION-CELLS
AMYLOID-BETA PEPTIDES
ALZHEIMERS-DISEASE
EXPERIMENTAL GLAUCOMA
TRANSGENIC MICE
MOUSE MODEL
APOPTOSIS
TIME
NECROSIS
NEUROPROTECTION
Alzheimer Disease
Amyloid beta-Peptides
Animals
Apoptosis
Disease Models, Animal
Dizocilpine Maleate
Mice
Necrosis
Neurodegenerative Diseases
Retinal Ganglion Cells
Publication Status: Published
Article Number: e3
Online Publication Date: 2010-01-14
Appears in Collections:Division of Surgery
Faculty of Medicine



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