Abstract :
[en] Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly population in developed countries. 90% of all vision loss due to AMD result from the exudative form of this pathology, which is characterized by a choroidal neovascularization (CNV). Currently, diagnosis of AMD relies on ophthalmologic exams and treatments of the exudative form are based on the use of anti-angiogenic drug targeting vascular endothelial growth factors. Despite these advance, several clinical challenges have to be overcome. Among those, the identification of biomarkers that could allow to refine patient stratification, to follow disease progression and evaluate responses to treatment are mandatory. For this purpose, we decide to apply NMR-based metabolomics approach on both AMD patients and on a laser-induced murine choroidal neovascularization experimental model.
In the clinical study, the metabolomics approach does not allow a complete differentiation between control and AMD patients. However, focusing only on AMD group, a clear-cut separation between active and non-active phases could be highlighted.
In the mice model, discrimination between laser-induced and control mice occurs only when CNV is installed.
In both human and animal studies, lactate and lipoprotein profile were identified as the main biomarkers.
Mechanistically, we demonstrated that lactate, plays a critical role in the onset of the inflammatory and angiogenic phases and could be correlated with the CNV development. Then, controlling lactate level appears as a new therapeutic approach of AMD
On the other hand, lipoprotein profile is of particular interest for patient follow-up. Indeed, evaluation of lipoprotein profile change trough a simple methods allowed us to establish clear modification of profiles according to the active or non-active status of the patient and to the induced or non-induced status of the mice.
This work focuses on the lipoprotein profile and on the development of a methodology that could be used to characterize and compared the different profiles in the human and the mice studies.
