FP7Individual fellowship2009–2011

AMD BIOMARKERS · Biomarkers in age-related macular degeneration

FP7 — People (Marie Curie Actions)

Duration
2009-06-01 → 2011-05-31
EU contribution
€171,301
Participants
1
Scheme
MC-IEF

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Results in brief

Biomarkers in age-related macular degeneration

Project context Degenerative retinal diseases are the most common cause of blindness in the Western world. In particular, age-related macular degeneration (AMD) mostly affects the elderly and inherited retinal diseases are the most common cause for sight loss in the 20-60-year-old population. People with severe sight loss in both eyes, e.g. due to AMD, are severely affected in their quality of life. It has been shown that they are affected as much as those who have had a stroke, severe cardiovascular disease, coronary artery disease or cancer. To date, there is no effective therapy for certain AMD sub-forms and for a large number of inherited retinal diseases. The socio-economic impact underlines the need for the development of better diagnostic approaches to identify affected patients early and for an improved understanding of degenerative retinal diseases in order to develop new therapies. Project results We have investigated certain aspects of AMD pathophysiology that may play an important role as biomarkers and/or in the future development of novel therapies. Examples are the identification of a genetically controlled systemic activation of the innate immune system in AMD patients, or the mechanistic insight into innate immune responses to oxidative stress, both of which may be exploited in the future prevention of and therapy for AMD. We have studied biomarkers for retinal disease in animal models using novel imaging techniques. In-vivo confocal autofluorescence imaging of the retina has been optimised in mice and applied to models of human retinal degeneration. The technique has been applied in a mouse model for AMD and Stargardt disease and will allow a clinically meaningful assessment of novel therapies in preclinical studies. We have also developed and investigated a combination of structural and functional assessments of the human retina. Surrogate end points derived from such multi-modal structure-function computation and correlation may become highly relevant in future clinical trials. Such an approach of investigating treatment effects may decrease the number of patients and the duration of clinical trials, and thus may lead to a faster availability of novel therapies. Also, such novel imaging techniques were applied to further investigate the phenotype of a number of degenerative retinal diseases, showing that biomarkers derived from applying such techniques are useful for diagnosis and disease monitoring as well as in the assessment of treatment effects. PProject impacts The project has already led to new scientific projects in European collaboration and the spread of specialised knowledge from one centre to another. A collaboration between the host institution in the UK and my future academic institution has already been agreed upon. In addition, it is planned to foster a further academic exchange between the two institutions with their different specialised knowledge.

Data: CORDIS, © European Union

Project objective

Age-related macular degeneration (AMD) is the leading cause of blindness in all populations of European origin with a large socio-economic impact on health systems. Better understanding of the disease should allow to improve diagnosis and disease monitoring and to develop new therapies. Aging and genetic predisposition are the most important risk factors for AMD. Many of the risk genes code for proteins of the innate immune system. Consistently, altered blood concentrations of immune-proteins have been detected in AMD strongly suggesting that such proteins can be used as biomarkers for AMD. Other proteins have also been found to be altered in AMD. We hypothesise that a combination of biomarkers, such as complement activation products, cytokines and elastin degradation products, are highly discriminative for AMD and allow an estimation of disease progression. This would enable clinicians to better allocate personal and financial resources for early identification and therapeutic monitoring of AMD patients at risk. Protein microarray will be used to quantify a large number of biomarkers. Logistic models will define the most relevant proteins and correlation with genetic markers will define biologically meaningful genetic polymorphisms. The relevant proteins will be analysed in blood samples of a large population based cohort. In 2008, all of these patients are being re-examined 6 years after baseline. The six year gap allows a significant number of patients with early AMD at baseline to have developed end-stage AMD, allowing the correlation of baseline systemic biomarkers with disease progression. The relevant biomarkers will furthermore be studied in animal models for AMD in order to better characterize and compare these models regarding systemic alterations observed in AMD patients.

Original text from CORDIS.

Participants

  • THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD · OxfordCoordinatorUnited Kingdom

Links

Data: CORDIS, © European Union