title: Imaging multiple phases of neurodegeneration: a novel approach to assessing cell death in vivo.
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.
authors.affiliation: UCL Institute of Ophthalmology, University College London, London, UK. M.Cordeiro@ucl.ac.uk
authors.forename: M F
authors.initials: MF
authors.lastname: Cordeiro
authors.forename: L
authors.initials: L
authors.lastname: Guo
authors.forename: K M
authors.initials: KM
authors.lastname: Coxon
authors.forename: J
authors.initials: J
authors.lastname: Duggan
authors.forename: S
authors.initials: S
authors.lastname: Nizari
authors.forename: E M
authors.initials: EM
authors.lastname: Normando
authors.forename: S L
authors.initials: SL
authors.lastname: Sensi
authors.forename: A M
authors.initials: AM
authors.lastname: Sillito
authors.forename: F W
authors.initials: FW
authors.lastname: Fitzke
authors.forename: T E
authors.initials: TE
authors.lastname: Salt
authors.forename: S E
authors.initials: SE
authors.lastname: Moss
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D051379:Mice; D009336:Necrosis; D019636:Neurodegenerative Diseases / Q000175:diagnosis*; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology
chemical_list: D016229:Amyloid beta-Peptides; D016291:Dizocilpine Maleate