Age-related macular degeneration

Age-related macular degeneration (AMD) is a complex degenerative disorder of the central retina, in which individual genetic variants, as well as environmental and lifestyle factors contribute to disease risk. Currently, the molecular mechanisms of disease pathology are not fully understood, although irregularities in complement system regulation, extracellular matrix remodeling, and lipid metabolism are suspected to play major roles. At our Institute, several projects address both genetic risk factors and molecular pathomechanisms of AMD, using a wide methodological spectrum. Big data analysis protocols are applied to bioinformatically elucidate the molecular mechanisms underlying AMD, with a current focus on methylation and gene expression regulation. In vitro and in vivo studies address an impact of specific AMD-associated genetic variants on epigenetic gene expression regulation by microRNAs, and on the functionality of candidate proteins, linked to AMD pathogenesis in scientific disclosures before. To mimic genetic and environmental risk factors in vitro, a repository of patient-derived induced pluripotent stem cell (iPSC) lines belonging to different genetic AMD risk groups was generated and different oxidative stress models were established. The results of these studies shall expand our knowledge on initial pathomechanisms in AMD pathogenesis and ultimately explore the opportunity for novel therapeutic options.


Selected publications:

  • Strunz T, Lauwen S, Kiel C; International AMD Genomics Consortium (IAMDGC), Hollander AD, Weber BHF. A transcriptome-wide association study based on 27 tissues identifies 106 genes potentially relevant for disease pathology in age-related macular degeneration. Sci Rep. 2020 Jan 31;10(1):1584. doi: 10.1038/s41598-020-58510-9
  • Liao DS, Grossi FV, El Mehdi D, Gerber MR, Brown DM, Heier JS, Wykoff CC, Singerman LJ, Abraham P, Grassmann F, Nuernberg P, Weber BHF, Deschatelets P, Kim RY, Chung CY, Ribeiro RM, Hamdani M, Rosenfeld PJ, Boyer DS, Slakter JS, Francois CG. Complement C3 Inhibitor Pegcetacoplan for Geographic Atrophy Secondary to Age-Related Macular Degeneration: A Randomized Phase 2 Trial. Ophthalmology. 2020 Feb;127(2):186-195. doi: 10.1016/j.ophtha.2019.07.011