Characterization of erythropoieisis abnormalities in Central Retinal Vein Occlusion patients
Responsable de l’encadrement : Dr Sandrine Laurance
Tél : 01 44 49 30 71
Résumé du projet
Central Retinal Vein Occlusion (CRVO) is a leading cause of blindness affecting mainly the elderly (onset at the age of 50 years) with a prevalence estimated at 0.8‰ in France. It is the 2nd most frequent retinopathy. CRVO is characterized by the presence of retinal hemorrhages and the appearance of venous dilation/tortuosity. Fluorescein angiography shows that the occlusion is driven by a slowdown of the venous flow in the absence of a thrombus formation. This observation combined to the lack of efficiency of the conventional anti-coagulant therapy makes CRVO a vascular non-thrombotic disease with the occlusion being induced by alterations of the vessel wall and of the erythroid lineage as it is the case in sickle cell disease, a genetic hemoglobin disorder.
Our laboratory is devoted to characterization of RBCs in health and disease. In this context, we were the first to investigate the potential role of erythroid lineage in CRVO occurrence. We have shown that CRVO red blood cells (RBCs) exhibit higher adhesion to endothelial cells (ECs) in approximately 50% of CRVO patients. In addition, we have shown that not only circulating RBCs are affected in CRVO pathophysiology but also erythropoiesis, the process of erythroid differentiation.
up to 50% of CRVO patients exhibit in vitro a successful erythroid differentiation, with hemoglobin rich RBCs as end product, in the absence of Epo although this latter is essential to erythropoiesis. The mechanism underlying this surprisingly Epo-independent differentiation in CRVO is not related to any identifiable myeloproliferative disorders and remains to be elucidated.
The purpose of the master project will be to actively participate to the investigation on the molecular mechanism leading to the CRVO abnormal erythropoiesis. To this aim, the student will work on patients’ blood samples from the Ophtalmopôle at Cochin Hospital and will perform in vitro erythropoiesis. A multidisciplinary approach ranging from flow cytometry, cell sorting to western blot and confocal microscopy will be used to decipher the pathological mechanism underlying the Epo-independent erythropoiesis. Characterizing the defects of CRVO erythroid lineage will lead to the identification of novel therapeutic strategies that are lacking so far.
Our lab is dedicated to the RBC from it physiological to its pathological state and thus owns a strong expertise on its cellular and molecular biology. It will provide to the student a strong expertise of platform facilities (red cell clinic, proteomic, imaging and flow cytometry). The large panel of experimental methodology, the dynamic scientific environment as well as the innovative scientific topic will allow the master student to get very good skills in a wide range of experiments, to develop his/her presentation and writing skills.
Dernières Publications en lien avec le projet :
El Hoss, Haematologica, 2020
Wautier, J Thromb Haemost, 2011
Heron, Ophtalmology, 2007
Ce projet s’inscrit-il dans la perspective d’une thèse :
oui o non x
Equipe d’Accueil : Inserm UMR_1134
Intitulé de l’Unité : Biologie Intégrée du Globule Rouge
Nom du Responsable de l’Unité : Dr Yves Colin Aronovicz
Nom du Responsable de l’Équipe : Pr Caroline Le Van Kim
Adresse : 6 rue Alexandre Cabanel 75015 Paris