Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries; with the aging population, the negative health impacts and costs of the disease will increase dramatically over the next decade. Although the exact cause of AMD is unknown, genetic studies have implicated the complement system as well as other immune responses in disease pathogenesis and severity. Furthermore, histologic studies have shown the presence of macrophages, lymphocytes, and mast cells, as well as fibroblasts, in both atrophic lesions and with retinal neovascularization. This review summarizes discussions from the fifth annual conference of the Arnold and Mabel Beckman Initiative for Macular Research by the Inflammation and Immune Response Task Force. These deliberations focused on the role of inflammatory immune responses, including complement, inflammasomes, adaptive immune responses, and para-inflammation, unanswered questions and studies to address these questions, and potential immune-related therapeutic targets for AMD. 1. Introduction Age-related macular degeneration (AMD) is the leading cause of central vision loss in developed countries. The most recent data suggest that more than 3 million people in the United States will be affected by the disease by 2020 [1]. The disease affects the choriocapillaris, Bruch’s membrane and the retinal pigment epithelium, with dysfunction and death of overlying photoreceptors. In addition to age, risk factors for the disease include both environmental and epidemiologic factors. Specific disease associations include smoking, light exposure, obesity, and race [2]. Recent genetic studies have implicated roles for the immune system, particularly abnormalities in the complement system, in disease pathogenesis, and severity. Although patients with AMD do not have signs of overt ocular inflammation, histologic studies have shown the presence of macrophages, lymphocytes, and mast cells, as well as fibroblasts, associated with both atrophic lesions and with neovascularization of the retina [3]. Importantly, the retina is a highly metabolically active tissue, with requirements to mediate photoreceptor turnover. As the retina ages, it may be less able to handle these metabolic requirements. Immunologically active deposits called drusen that contain lipids, complement, and other potentially immune activating substances may act as additional triggers for immune responses in the eye. Other inflammatory initiators include oxidative stress and secondary mediators of inflammation such as cytokines. On the other hand, the
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