Aufklärung der Auswirkungen von C3b-Abbauprodukten auf die mikrogliale Aktivierung und Neurodegeneration in der Pathogenese der altersbedingten Makuladegeneration (AMD)

01.08.2024 bis 30.07.2027

Age-related macular degeneration (AMD) is a degenerative eye disease causing blindness in the elderly population. The role of complement over-activation in AMD has given rise to many complement targeting therapeutics being developed. However, existing therapeutics have limited efficacy, probably because they have been solely focused on switching off complement turnover rather than also addressing the downstream opsonisation effect of C3b breakdown products on retinal tissue remodelling through microglia/RPE mediated phagocytosis. Remarkably, we still do not fully understand the effect of each opsonin on microglia or RPE cell molecular pathways, and therefore how best to ‘switch-off’ the subsequent excessive tissue remodelling observed in AMD. Prof. Simon Clark aims to investigate the intricate molecular consequences on microglia/RPE after engagement with each C3b breakdown opsonin (i.e. C3b>iC3b>C3dg>C3d each showing decreasing opsonisation potency).