Periodic Reporting for period 2 - Retina Rhythm (Investigating the role of the inner retina in age-related macular degeneration (AMD))
Berichtszeitraum: 2022-01-01 bis 2023-06-30
Why is this important for society?: Over 224,000 Irish people and 40 million people worldwide are affected by severe vision loss where they would be considered legally blind. The number of people affected by blindness is increasing, largely due to our ageing population. The Economic Cost and Burden of Eye Diseases and Preventable Blindness in Ireland report was released in April 2014 by the National Vision Coalition, part of a pan-European study of 16 countries by Deloitte, an alliance of ophthalmology healthcare professionals, those working in the sight loss community, and service users (http://www.ncbi.ie/about- ncbi/national-vision-coalition/). People should not have to suffer avoidable sight loss, the vision loss associated with retinal diseases as outlined here should be avoidable with partner diagnostic and personalized treatment using our innovative approaches. The burden of blindness/sight loss on healthcare services stretches beyond Ophthalmology care as people with vision loss are up to eight times more likely to fracture a hip, three times more likely to be depressed, and admission to nursing homes takes place up to three years earlier. There will be a significant financial benefit if sight loss can be avoided. In addition, cost to the State increases significantly if a person progresses from being visually impaired (€1.7K per person per annum) to being blind (€21K per person per annum). It has been estimated that 123 million workdays are lost per year in Europe, while in Ireland 2.1 million healthy days are lost per annum as a consequence of vision impairment and blindness.
What are the overall objectives? We have 3 main objectives in our project. The first is to prove that the blood vessels of the inner retina are centrally involved in initiating pathology in AMD. The second objective is to explore novel therapeutic strategies to regulate blood vessels of the retina to prevent disease in animal models. Finally, we are also conducting a large clinical research project whereby we take very detailed pictures of the blood vessels of the retina in patients living with AMD. Overall, we seek to gain an in depth understanding of what drives AMD pathology and how we can design drugs of the future to treat this debilitating blindness.
1. We have established 3 different animal models of AMD. These models were created by decreasing the levels of a key component of the blood vessels in the retina termed claudin-5. In tandem with making the blood vessels int he retina marginally "leaky", when we supplement the animals' diet with a high cholesterol diet, they develop a pathology remarkably similar to AMD.
2. Using these models, we are now in the process of developing a gene therapy based approach to restore the integrity of the blood vessels and thereby prevent the onset of AMD-like pathology. This is the first step int he pathway of development of a novel form of therapy for early AMD.
3. We have established a clinical research facility in Dublin that allows us to recruit patients who have been diagnosed with various stages of AMD. We are able to take very high resolution images of the retinas of these patients, and using novel software developed as part of this ERC project, we are able to determine the status and integrity of the blood vessels with great accuracy. This serves 2 purposes. It may eventually allow for accurate prognostic readouts for patients and secondly, it it allowing us to gain an in-depth understanding of the role the inner retina and especially the inner retinal blood vessels play in AMD.
In the next 30 months, we will finalize our clinical research project and report on the largest study of its kind to date. We will also publish our work related to 3 new mouse models of AMD that will be of immense value to the vision research community. Finally, we will publish and share our newly developed software, Fluorescent Ocular Vasculature Analysis Software (FOVAS), which allows for the objective and quantitative assessment of blood vessel integrity in the retina of animals and humans.