A report from the National Eye Institute (NEI) in Bethesda, has highlighted a multi-pronged approach to support investments by NEI for AMD across basic and clinical trial research over the coming decade. The institute has outlined its commitment to provide invaluable resources to investigators to address complex blinding diseases and other retinal degenerative diseases. The report found that translational relevance was a key objective to expand NEI resources to uncover disease mechanisms and move experimental therapies into clinical trials. AMD’s prevalence is expected to double by 2050 and this will result in a significant public health burden over the coming decades which requires significant investment, even in the current economic challenges globally. In particular, the NEI have commented how their focus on “the advent of regenerative medicine and iPSC technologies, coupled with advances in clinical imaging, analytical, and other advanced technology herald a new frontier in vision research”.
According to their recent report, the NEI spent more than $1 billion (adjusted for inflation) from 2008 to 2017 to conduct studies to increase the role of research in understanding AMD pathology. The institute outlined “to be successful in treating and preventing AMD, we must tackle the problem along the continuum of supporting basic biology to clinical work and back again”. The study focused on the past, present and future of research on AMD activities showing from clinical characterization of disease and diagnosis to GWAS and whole genomic sequencing advances. In addition. AREDS and AREDS2 studies have expanded significantly over the previous decades and the newly created AMD Integrative Biology Initiative opened a further departure. This now progresses a more precise description of AMD disease pathobiology using genetic risk factors as sentinels for specific RPE signalling pathways and changes in RPE physiology. The NEI proposes this approach as a guide to the development of personalized therapies for AMD.
In brief, the NEI supports a “broad range of AMD research, both by individual independent investigators as well as through networks and consortia”. The International AMD Genomics Consortium, Age-Related Eye Disease Study, Age-Related Eye Disease Study 2 (AREDS2), and Comparison of AMD Treatments Trial legacy have presented an enormous body of work, with significant collaboration across US, EU and global expertise. A recent example highlighted the AMD Ryan Initiative Study aimed to unravel the clinical evolution of early AMD and the importance of reticular pseudo-drusen in predicting progression to advanced disease. This study will take place across 20 international clinical centres with >500 patients, including AMD patients with bilateral medium sized drusen, patients with reticular pseudo-drusen in the absence of large drusen, and further age-matched controls. Finally, NEI is to support AREDS2 participant-derived induced pluripotent stem cell (iPSC) lines linked with their associated genomic and phenotypic datasets. In this exciting initiative, as commented in the report, “these datasets will also be linked to the data obtained using their associated iPSC-derived cells (RPE, retina, choroid) and made publicly available”.