Description du projet
Régulation circadienne de la rétine: une nouvelle voie pour traiter la dégénérescence maculaire liée à l’âge?
L’absence de modèles de maladies pour la dégénérescence maculaire liée à l’âge (DMLA), l’une des principales causes de la cécité, a limité le développement de thérapies efficaces. Les chercheurs du projet Retina Rhythm, financé par l’UE, étudient la manière dont les vaisseaux sanguins de la rétine interne, dont les récentes découvertes ont prouvé le grand dynamisme, sont impliqués dans le développement et la pathologie de la DMLA. Leurs expériences dévoileront l’impact de la régulation circadienne dans les premiers stades de la maladie et jetteront les bases de nouvelles interventions thérapeutiques contre la DMLA. Plus important encore, l’identification des principaux moteurs précoces du développement de la DMLA permettra d’améliorer le diagnostic rapide et de contribuer à identifier les personnes à risque.
Objectif
Age-related macular degeneration (AMD) is the leading cause of irreversible central blindness in the world. The number of people with AMD is predicted to be 196 million by 2020, with an estimated 1 in 10 people over the age of 55 already showing early signs of the condition. Identifying those individuals at greater risk of disease progression is challenging and robust animal models of disease are delaying the development of therapeutics.
We have recently discovered that the blood vessels of the inner retina are highly dynamic and our data suggest that they play a central role in AMD development. I hypothesize, in contrast to studies to date, that the inner retina may be critical to the early stages of AMD onset. We have discovered that circadian regulation of the inner blood-retina barrier (iBRB) allows for replenishment and renewal of components of photoreceptor outer segments on a daily basis by a process we have termed Retinal Interstitial Kinesis (RIK).
Here, I propose that circadian mediated regulation of the inner retinal blood vessels is paramount in the early stages of AMD pathology. Our preliminary data suggests that circadian-mediated changes in the permeability of the iBRB can lead to an AMD-like phenotype in mice and non-human primates. I propose that re-establishing the dynamic cycling of the iBRB may represent a novel therapeutic strategy for the prevention and treatment of AMD.
Over the next 5 years, the central aims of Retina-Rhythm are to:
1. Develop and characterize newly established mouse and non-human primate models of AMD by disrupting circadian cycling of the iBRB.
2. Develop a novel AAV based vector with the ability to re-establish dynamic circadian cycling of the iBRB and treat AMD.
3. Prove that dysregulated circadian-mediated iBRB cycling mediates AMD pathology in human subjects.
Our goal: To determine the key early initiators of AMD and to develop the next generation of therapies for this devastating form of blindne
Champ scientifique
Programme(s)
Régime de financement
ERC-COG - Consolidator GrantInstitution d’accueil
D02 CX56 DUBLIN 2
Irlande