Imperial College London
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Professor M Francesca Cordeiro

Faculty of Medicine, Department of Surgery & Cancer

Chair in Ophthalmology (Clinical)
 
 
 
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Contact

 

m.cordeiro

 
 
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Location

 

Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Cordeiro:2017:brain/awx088,
author = {Cordeiro, MF and Normando, EM and Cardoso, MJ and Miodragovic, S and Jeylani, S and Davis, BM and Guo, L and Ourselin, S and A'Hern, R and Bloom, PA},
doi = {brain/awx088},
journal = {Brain},
pages = {1757--1767},
title = {Real-time imaging of single neuronal cell apoptosis in patients with glaucoma},
url = {http://dx.doi.org/10.1093/brain/awx088},
volume = {140},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Retinal cell apoptosis occurs in many ocular neurodegenerative conditions including glaucoma—the major cause of irreversibleblindness worldwide. Using a new imaging technique that we have called DARC (detection of apoptosing retinal cells), which untilnow has only been demonstrated in animal models, we assessed if annexin 5 labelled with fluorescent dye DY-776 (ANX776)could be used safely in humans to identify retinal cell apoptosis. Eight patients with glaucomatous neurodegeneration and evidenceof progressive disease, and eight healthy subjects were randomly assigned to intravenous ANX776 doses of 0.1, 0.2, 0.4 and0.5 mg in an open-label, phase 1 clinical trial. In addition to assessing the safety, tolerability and pharmacokinetics of ANX776, thestudy aimed to explore whether DARC could successfully visualize individual retinal cell apoptosis in vivo in humans, with theDARC count defined as the total number of unique ANX776-labelled spots. DARC enabled retinal cell apoptosis to be identified inthe human retina using ANX776. Single ANX776-labelled cells were visualized in a dose-dependent pattern (P5 0.001) up to 6 hafter injection. The DARC count was significantly higher (2.37-fold, 95% confidence interval: 1.4–4.03, P = 0.003) in glaucomapatients compared to healthy controls, and was significantly (P = 0.045) greater in patients who later showed increasing rates ofdisease progression, based on either optic disc, retinal nerve fibre layer or visual field parameters. Additionally, the DARC countsignificantly correlated with decreased central corneal thickness (Spearman’s R = 0.68, P = 0.006) and increased cup-disc ratios(Spearman’s R = 0.47, P = 0.038) in glaucoma patients and with increased age (Spearman’s R = 0.77, P = 0.001) in healthy controls.Finally, ANX776 was found to be safe and well-tolerated with no serious adverse events, and a short half-life (10–36 min).This proof-of-concept study demonstrates that retinal cell apopt
AU  - Cordeiro,MF
AU  - Normando,EM
AU  - Cardoso,MJ
AU  - Miodragovic,S
AU  - Jeylani,S
AU  - Davis,BM
AU  - Guo,L
AU  - Ourselin,S
AU  - A'Hern,R
AU  - Bloom,PA
DO  - brain/awx088
EP  - 1767
PY  - 2017///
SN  - 1460-2156
SP  - 1757
TI  - Real-time imaging of single neuronal cell apoptosis in patients with glaucoma
T2  - Brain
UR  - http://dx.doi.org/10.1093/brain/awx088
UR  - https://academic.oup.com/brain/article/140/6/1757/3755374
UR  - http://hdl.handle.net/10044/1/56603
VL  - 140
ER  -
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