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Poster (Scientific congresses and symposiums)
From Metabolomics to Identification of a new therapeutic approach for Age-Related Macular Degeneration (AMD)
Schoumacher, Matthieu; De Tullio, Pascal; LAMBERT, Vincent et al.
2016JFB 2016 : 30èmes Journées Franco-Belges de Pharmacochimie
 

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Keywords :
Métabolomic; AMD; NMR
Abstract :
[en] Age-related macular degeneration (AMD) is the leading cause of vision loss in the western world among people aged 50 or older. 90% of all vision loss due to AMD result from the exudative form, which is characterized by choroidal neovascularization (CNV). Age-related changes that induce pathologic CNV are incompletely understood and critical issues remain to be addressed. Metabolomics is defined as the comprehensive study of endogenous metabolites changes in various biological systems. This newly emerging “omic” science provides a unique opportunity to correlate variation of the metabolome with pathological occurrence or progression and/or to identify metabolites that are implicated in the disease. We apply a 1H NMR metabolomics approach on sera collected from AMD patient and healthy volunteers and form a mice model of laser-induced CNV which mimics the effect of exudative AMD. After post-processing treatments, the different spectra were analyzed by statistical discriminant methodologies (PCA, ICA, PLS-DA, O-PLS-DA). These approaches allow the differentiation between control and AMD patients and between laser-induced mice and the control mice group. Moreover, the same discriminating spectral zones have been identified in human and mice model, leading to the emergence of different putative biomarkers. Among these markers, lactate emerges as a key metabolite in both settings. Mechanistically, lactate produced locally and by inflammatory cells, plays a critical role in the onset of the inflammatory and angiogenic phases. In mice model of laser-induced CNV, normalization of circulating lactate by dichloroacetate a pyruvate dehydrogenase kinase (PDK) inhibitor, decreases CNV development. Our data support the innovative concept of lactate as a parainflammation- and angio-metabolite associated to AMD and CNV progression. Moreover, control of blood lactate level via inhibition of PDK provides new options for the treatment of exudative AMD. This study demonstrates the ability of metabolomics for drug target discovery and opens new perspectives for AMD treatment and patient follow-up.
Research center :
Centre Interfacultaire de Recherche du Médicament - CIRM
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Schoumacher, Matthieu ;  Université de Liège > Département de pharmacie > Chimie pharmaceutique
De Tullio, Pascal ;  Université de Liège > Département de pharmacie > Chimie pharmaceutique
Other collaborator :
LAMBERT, Vincent  ;  Centre Hospitalier Universitaire de Liège - CHU > Service d'ophtalmologie
Hansen, Sylvain ;  Université de Liège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Leenders, Justine ;  Université de Liège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Govaerts, Bernadette;  Université Catholique de Louvain - UCL > Institut de statistique
Pirotte, Bernard ;  Université de Liège > Département de pharmacie > Chimie pharmaceutique
RAKIC, Jean-Marie ;  Centre Hospitalier Universitaire de Liège - CHU > Service d'ophtalmologie
Noël, Agnès ;  Université de Liège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Language :
English
Title :
From Metabolomics to Identification of a new therapeutic approach for Age-Related Macular Degeneration (AMD)
Publication date :
May 2016
Number of pages :
A0
Event name :
JFB 2016 : 30èmes Journées Franco-Belges de Pharmacochimie
Event organizer :
Université d'Orléans
Event place :
Amboise, France
Event date :
25-27/05/16
Audience :
International
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Available on ORBi :
since 23 May 2016

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