C3a triggers formation of sub-retinal pigment epithelium deposits via the ubiquitin proteasome pathway.

ABSTRACT: The mechanisms that connect complement system activation and basal deposit formation in early stages of age-related macular degeneration (AMD) are insufficiently understood, which complicates the design of efficient therapies to prevent disease progression. Using human fetal (hf) retinal pigment epithelial (RPE) cells, we have established an in vitro model to investigate the effect of complement C3a on RPE cells and its role in the formation of sub-RPE deposits. The results of these studies revealed that C3a produced after C3 activation is sufficient to induce the formation of sub-RPE deposits via complement-driven proteasome inhibition. C3a binds the C3a receptor (C3aR), stimulates deposition of collagens IV and VI underneath the RPE, and impairs the extracellular matrix (ECM) turnover by

SUBMITTER: Fernandez-Godino R 

PROVIDER: S-EPMC6018664 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature