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Investigating the role of the inner retina in age-related macular degeneration (AMD)

Descrizione del progetto

Regolazione circadiana della retina: un nuovo percorso per trattare la degenerazione maculare legata all’età?

La mancanza di modelli di malattia per la degenerazione maculare legata all’età (AMD, age-related macular degeneration), uno dei principali fattori di cecità, ha impedito lo sviluppo di terapie. Gli scienziati del progetto Retina Rhythm, finanziato dall’UE, stanno studiando il modo in cui i vasi della retina interna, che recenti scoperte hanno dimostrato essere altamente dinamici, sono coinvolti nello sviluppo e nella patologia dell’AMD. I loro esperimenti sveleranno l’impatto della regolazione circadiana nelle prime fasi della malattia e getteranno le basi per nuovi interventi terapeutici contro l’AMD. È ancora più importante notare che l’identificazione dei primi fattori principali dello sviluppo dell’AMD migliorerà la diagnosi e contribuirà all’identificazione dei soggetti a rischio.

Obiettivo

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

Meccanismo di finanziamento

ERC-COG - Consolidator Grant

Istituzione ospitante

THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD, OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN
Contribution nette de l'UE
€ 1 999 455,00
Indirizzo
COLLEGE GREEN TRINITY COLLEGE
D02 CX56 DUBLIN 2
Irlanda

Mostra sulla mappa

Regione
Ireland Eastern and Midland Dublin
Tipo di attività
Higher or Secondary Education Establishments
Collegamenti
Costo totale
€ 1 999 455,00

Beneficiari (1)