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An eye on the future of inflammasomes and drug development in AMD

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Abstract

Age-related macular degeneration (AMD) is the leading cause of central vision loss worldwide. While activation of the immune system has been implicated in disease progression, the pathways involved remain relatively unclear. Typically, inflammatory responses are caused as a result of pathogenic infection. However, in chronic conditions, like AMD, a form of ‘sterile’ inflammation can exist in localised areas of the body in response to modified host-derived elements and particulate matter accumulation, due to the activation of a complex termed the ‘inflammasome’. Inflammasomes control the activity of two major pro-inflammatory cytokines, namely, interleukin (IL)-1β and IL-18, by allowing for their cleavage from inactive pro-forms into mature cytokines. The major pathological hallmark common to both ‘dry’ and ‘wet’ AMD is the presence of extracellular deposits, known as drusen, below the retinal pigment epithelium in the macula of the eye. Past studies have shown that host-derived particulate matter such as amyloid deposits and atherosclerotic plaques can be ‘sensed’ by the NLRP3-inflammasome causing cleavage of pro-IL-1β and pro-IL-18. We have recently reported that the NLRP3-inflammasome can also ‘sense’ drusen isolated from human AMD donor eyes and that IL-18 protects against the development of choroidal neovascularisation in a model that mimics ‘wet’ AMD. In fact, since then, a number of studies have reported roles for the NLRP3-inflammasome in AMD. This review will focus on describing, comparing and contrasting these reports and analyzing the potential for manipulating the NLRP3-inflammasome as a therapy for AMD.

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Authors and Affiliations

  1. Ocular Genetics Unit, Trinity College Dublin, Lincoln Place Gate, Dublin 2, Ireland

    Matthew Campbell

  2. Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin 2, Ireland

    Sarah L. Doyle

  3. National Childrens Research Centre, Our Ladys Childrens Hospital, Crumlin, Dublin 12, Ireland

    Sarah L. Doyle

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  1. Matthew Campbell
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Campbell, M., Doyle, S.L. An eye on the future of inflammasomes and drug development in AMD. J Mol Med 91, 1059–1070 (2013). https://doi.org/10.1007/s00109-013-1050-0

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