Central Retinal Vein Occlusion

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. The disease 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. 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 by showing that CRVO 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. We did observe that 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. Besides RBCs, our group is also investigating the vessel wall alterations occurring in CRVO. Subsequently to an exome study performed in CRVO patients, we identified several gene candidates known to play a major role in vascular homeostasis and angiogenesis. Validation of the functional relevance of these mutations will provide new insights in the regulation of vascular homeostasis and how it will impact interactions between the vessel wall and circulating erythroid cells.

Overall, our project aims to provide a comprehensive view of CRVO that will improve the understanding of the disease and consequently the development of new treatment approaches for CRVO patients affected by one of the major causes of blindness.