Pre-diagnosis Biomarker Discovery for Age-Related Macular Degeneration

The goal of the project is to identify pre-diagnosis plasma biomarkers for AMD, i.e., markers that can be measured in plasma samples from healthy donors and may predict which donors will get AMD in the following years. We will use approx.150 plasma samples collected and stored at the Biome MSSM Biorepository, from healthy, non-AMD donors, which eventually became diagnosed with AMD 2-8 years after the blood donation. These samples will be compared to samples from donors that did not develop AMD after a similar number of years. We will use two strategies. The first strategy (Aim 1) consists of analyzing the protein composition of plasma samples using the SOMAscan platform, which allows quantitation of approx. 7000 proteins. In addition, we will investigate whether pre-diagnostic differences exist in the optical spectra generated by Fourier Transform Infrared (FTIR) spectroscopy. Aim 2 is based on the hypothesis that some post-diagnostic biomarkers, shown by published studies to robustly differentiate healthy donors from AMD patients, reflect differences that pre-exist years before the donors are diagnosed. We will investigate, using the BioMe plasma samples, whether the differences exist years before the disease develops. As most BioMe donors have been fully genotyped, genetic information will be also included in the effort to find pre-diagnostic biomarkers. Regarding the potential impact of the study, a large-scale effort is underway for years to find dietary supplements and other agents that could prevent AMD. Such studies involve administration for years of supplements to relatively large numbers of subjects that do not have yet AMD and waiting for years to determine if the proportion of persons that develop the disease is reduced. Development of predictive biomarkers could enormously simplify such efforts, by assessing the immediate effect of the supplements on the biomarkers. At the level of individual subjects, if protective interventions are found, the pre-diagnostic markers will help detect the persons for which the interventions are necessary.