CV Science

Emeline Nandrot Physiology of the retinal pigment epithelium and associated pathologies

Course and current status

PROFESSIONAL POSITIONS  

2008-present: Institut de la Vision, Therapeutics Department, Paris, France. Team Leader, CNRS CR1 permanent position.

2002-2007: Dyson Vision Research Institute, Weill Medical College of Cornell University, New York, USA.

1998-2002: Centre de Recherches Thérapeutiques en Ophtalmologie CERTO, Necker Medicine Faculty, Paris, France.

1996-1997: Service de Recherche en Hémato-immunologie, St Louis Hospital, Paris, France. 

1995: Généthon, Evry, France.

DEGREES

1998-2002: PhD degree magna cum laude, Human Genetics. Denis Diderot University, Paris VII.

1997: M. S. degree, Human Genetics. Denis Diderot University, Paris VII.

1996: B. S. degree, Biology and applied Genetics. Denis Diderot University, Paris VII.

1992: Baccalaureate, mathematics. 

Scientific summary

At the back of the eye lie cells from the retinal pigment epithelium (RPE). RPE functions are numerous and all crucial for vision: supply in nutrients, ions and oxygen to photoreceptors, retinal homeostasis, renewal of photopigments, etc.

Adjacent to RPE cells, photoreceptors initiate the visual signaling reaching the brain in a specific compartment constituted of membranous disks containing photosensitive molecules and named photoreceptor outer segments (POS). POS are submitted to a strong oxidative stress due to their constant exposure to light rays. In order to limit this stress, POS are permanently renewed and their most-aged distal part is shed following a circadian rhythm. POS are phagocytosed by RPE cells at a level of around 30 POS per RPE cell. Thus RPE cells represent the busiest phagocytes in the body.

Complete absence or deregulated retinal phagocytosis lead to early or late vision loss respectively, in rodent models as well as in human patients. Indeed, mutations in patients affected by rod-cone dystrophies (atypical retinitis pigmentosa) as well as by cone-rod dystrophies with macular lesions. Retinal phenotypes observed in rodent models resemble phenotypes observed in human patients such as retinitis pigmentosa or age-related macular degeneration, first cause of blindness in people over 50 years. These date pinpoint the importance of understanding retinal phagocytosis mechanisms in order to envision treatments for these blinding diseases for which no cure exists so far.

Projects in the laboratory aim at caracterizing the molecular mechanisms ruling the daily rhythmic disposal of shed POS. We previously identified the alphavbeta5 integrin receptor-ligand proteins synchronizing this rhythmic phagocytosis and the MerTK receptor necessary to subsequent POS internalization. These mechanisms are closely related to those used by macrophages to discard apoptotic cells. However, in the retina photoreceptors and RPE cells are permanently in close contact, underlying the strict regulation of this function at the molecular level. We recently showed that this tissue specificity lies in the way ligands for MerTK work in the retina both at the functional and circadian expression pattern levels. We also identified new families of receptors that appear to be implicated in this phagocytic process. Current projects aim at characterizing the regulation of the phagocytosis receptors activity and their associated signaling pathways.

In parallel, we are also interested in understanding why mutations in ubiquitous splicing factors only lead to retinitis pigmentosa phenotypes. Our current projects aim at characterizing processes deregulating some circadian functions of RPE cells and mechanisms producing oxidative stress in various cellular areas (mitochondria, endoplasmic reticulum...).