Role of inflammation in the pathogenesis of age-related macular degeneration

This article aims to review the role of inflammation in the pathogenesis of age-related macular degeneration. Besides environmental factors, a direct link to genetics in general and/or genetics of inflammatory pathways could be shown to contribute to both the initiation and propagation of the disease. The complement system with the Y402H variant of the complement factor H gene as one of the key factors plays a central role. A defect in the control mechanism leads to an activation in genetically predisposed individuals. The LOC387715/ARMS2 and HTRA1 genes, as well as certain chemokines and their receptors, especially the CX3CR1 chemokine receptor and the Toll-like receptors, are associated with the development of age-related macular degeneration. Among all inflammatory cells and mediators, macrophages deserve special attention. They have been shown to express both proinflammatory and angiogenic factors, such as VEGF and many others that have been identified in choroidal neovascularization membranes. However, there are controversial reports on the actual role of these inflammatory cells, as well as on the role of C-reactive protein. An additional mechanism that is directly related to inflammation is oxidative stress via the release of oxygen free radicals – a phenomenon that, to a certain extent, occurs in every mammalian organism – which may be increased in the aging body, thereby leading to oxidative tissue damage. This damage seems to be a crucial trigger for age-related macular degeneration via both direct damage of unsaturated fatty acids and activation of inflammatory pathways. Polyunsaturated fatty acids, major molecules of the photoreceptor outer segments, are highly susceptible to oxidation processes.