Donders Institute for Brain, Cognition and Behaviour
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Thesis defense Erkin Acar (Donders series 547)

11 March 2022

Promotor: Prof. A.I. den Hollander 
Co-Promotor: Dr. T.E. Galesloot

Omics studies in age-related macular degeneration

Age-related macular degeneration (AMD) is a progressive eye disease which is the most common cause of blindness in elderly population in the western world. AMD is a multifactorial disease where genetics and environmental factors both contribute to the risk of getting AMD. In this thesis, we approached AMD from both sides of the coin to understand it better. We have identified several new genetic variants that showed association with AMD. We expanded our work to investigate the combined effect of the genetic variants on the predefined genomic regions. These analyses resulted in novel candidate genes and genomic regions that should be followed up by future studies. Aside from the genetics part, we also investigated the metabolites of the AMD patients which were measured from the blood samples of the volunteering AMD patients and healthy controls. We identified several lipid measurements to be associated with AMD, where bigger HDL particles showed increased levels in AMD patients. These metabolites were further evaluated within different stages of AMD, where amino acids were found to be associated with late stage of the disease while lipid measurements were associated with early to intermediate stages of the disease. Known genetic variants were also tested for an effect on the metabolites, and only the variants in the lipid pathway genes showed significant associations. Lastly, complement pathway proteins in the immune system showed connections with metabolites that were associated with AMD. We have measured some of these complement pathway proteins and tested their connections in AMD, and AMD related genetic variants. While the proteins did not show a statistically significant associations with AMD, several AMD associated genetic variants were found to have a connection with these proteins. All of these findings together provide a better understanding of AMD in different biological levels. If the findings of these studies can be replicated in the future studies, the results can be translated into potential targets for drugs or lifestyle changes can be advised for lower AMD risk for the patients with family histories of AMD.