Project description
Circadian regulation of the retina: novel route to treat age-related macular degeneration?
The lack of disease models for age-related macular degeneration (AMD), a key cause of blindness, has hampered the development of therapeutics. Scientists of the EU-funded Retina Rhythm project are investigating how blood vessels of the inner retina, which recent discoveries have proven is highly dynamic, are implicated in AMD development and pathology. Their experiments will unveil the impact of circadian regulation in the early stages of the disease and set the ground for new therapeutic interventions against AMD. More importantly, the identification of key early drivers of AMD development will improve prompt diagnosis and help identify individuals at risk.
Objective
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
Fields of science
Programme(s)
Funding Scheme
ERC-COG - Consolidator GrantHost institution
D02 CX56 DUBLIN 2
Ireland