gms | German Medical Science

Progression of age-related macular degeneration (AMD) includes hallmarks of retinal pigment epithelium and photoreceptor loss accompanied by unchecked immune response and degeneration or pathological angiogenesis. While the current paradigm converges to associate complement dysregulation and inflammasome activation as major components of immune responses, we interrogate the specific mechanisms of action of macrophage and myeloid cells within the retina. This includes introducing the notion of a protective parainflammatory response. To that end we have shown how macrophages are early infiltrating cells that engulf dying RPE and drive angiogenesis and that this response may be subverted through cytokine modulation ((L-4, IL-33) of macrophage function or through activation of inhibitory receptors (CD200R). Furthermore our investigations have shown that it is the nature of RPE degeneration (oxidative stress, bio-energetic switching or impaired autophagy) that differentially regulate macrophage phenotype and function.