Immunological Aspects of Age-Related Macular Degeneration

Increasing evidence over the past two decades points to a pivotal role for immune mechanisms in age-related macular degeneration (AMD) pathobiology. In this chapter, we will explore immunological aspects of AMD, with a specific focus on how immune mechanisms modulate clinical phenotypes of disease and severity and how components of the immune system may serve as triggers for disease progression in both dry and neovascular AMD. We will briefly review the biology of the immune system, defining the role of immune mechanisms in chronic degenerative disease and differentiating from immune responses to acute injury or infection. We will explore current understanding of the roles of innate immunity (especially macrophages), antigen-specific immunity (T cells, B cells, and autoimmunity), immune amplifications systems, especially complement activity and the NLRP3 inflammasome, in the pathogenesis of both dry and neovascular AMD, reviewing data from pathology, experimental animal models, and clinical studies of AMD patients. We will also assess how interactions between the immune system and infectious pathogens could potentially modulate AMD pathobiology via alterations in in immune effector mechanisms. We will conclude by reviewing the paradigm of “response to injury,” which provides a means to integrate various immunologic mechanisms along with nonimmune mechanisms of tissue injury and repair as a model to understand the pathobiology of AMD.