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Abstract #46318 Published in IGR 13-2

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

Cordeiro MF; Guo L; Coxon KM; Duggan J; Nizari S; Normando EM; Sensi SL; Sillito AM; Fitzke FW; Salt TE
Cell Death and Disease 2010; 1: e3


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.

M. F. Cordeiro. Glaucoma and Retinal Neurodegeneration Research Group, UCL Institute of Ophthalmology, University College London, Bath Street, London EC1V 9EL, United Kingdom. Email: M.Cordeiro@ucl.ac.uk


Classification:

3.13.3 RGC Imaging (Part of: 3 Laboratory methods > 3.13 In vivo imaging)
11.8 Neuroprotection (Part of: 11 Medical treatment)



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