Serum level of terminal complement complex (TCC) in patients with AMD

Age-related macular degeneration (AMD) is a leading causes for vision loss in industrialized countries. Different types of translational research indicate that chronic inflammation drives the disease in the outer retina affecting photoreceptors, retinal pigment epithelium (RPE) and the choroid. Along with this, genetic analysis identified genes of components of the complement system with risk association for AMD. Polymorphisms in the complement gene C9, which’s gene product is part of the terminal complement complex (TCC), showed risk association and functional changes of TCC in the serum of AMD patients. TCC might reduce the viability of RPE cells with subsequent loss of photoreceptor cells and loss of vision as membrane attack complex. Therefore, we compared the TCC levels in AMD patients with aged-matched controls and found in general in AMD patients increased serum TCC levels. However, these levels did not differ among patients that carry the risk haplotypes for the complement factor CFH or ARMS2. Exposing RPE cells to patients’ sera changed the immunogenic phenotype towards a pro-inflammatory profile in gene expression and secretion instead of inducing cell death. Thus, our study implies a more general role of TCC in AMD and closes the gap between systemic changes and local inflammation.