Descripción del proyecto
La regulación circadiana de la retina: ¿una nueva vía para tratar la degeneración macular asociada a la edad?
La carencia de modelos patológicos para la degeneración macular asociada a la edad (DMAE), una de las principales causas de ceguera, ha obstaculizado el desarrollo de medicamentos. Los científicos del proyecto Retina Rhythm, financiado con fondos europeos, investigan la relación entre los vasos sanguíneos de la retina interna —que en estudios recientes han demostrado ser altamente dinámicos— con el desarrollo y la patología de la DMAE. Sus experimentos permitirán dilucidar los efectos de la regulación circadiana en los estadios iniciales de la DMAE y establecerán la base para el desarrollo de nuevas intervenciones terapéuticas para esta enfermedad. Es más, la identificación de los principales factores responsables del curso de la DMAE mejorará el diagnóstico precoz y ayudará a identificar personas en riesgo.
Objetivo
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
Ámbito científico
Programa(s)
Régimen de financiación
ERC-COG - Consolidator GrantInstitución de acogida
D02 CX56 DUBLIN 2
Irlanda