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As of today, for the majority of patients, no treatment exists. Multiple genetic and biochemical studies have shown a strong association with components in the complement system and AMD, and evidence suggests a major role of remodeling of the extracellular matrix underlying the outer blood\/retinal barrier. As part of the innate immune system, the complement cascade acts as a first\u2010line defense against pathogens, and upon activation, its amplification loop ensures a strong, rapid, and sustained response. Excessive activation, however, can lead to host tissue damage and cause complement\u2010associated diseases like AMD. AMD patients present with aberrant activation of the alternative pathway, especially in ocular tissues but also on a systemic level. Here, we review the latest findings of complement activation in AMD, and we will discuss in vivo observations made in human tissue, cellular models, the potential synergy of different AMD\u2010associated pathways, and conclude on current clinical trials and the future outlook.<\/jats:p>","DOI":"10.1111\/imr.13145","type":"journal-article","created":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T15:30:05Z","timestamp":1665588605000},"page":"279-297","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Age\u2010related macular degeneration: A disease of extracellular complement amplification"],"prefix":"10.1111","volume":"313","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3705-3371","authenticated-orcid":false,"given":"Sarah","family":"de Jong","sequence":"first","affiliation":[{"name":"Department for Ophthalmology University Eye Clinic, Eberhard Karls University of T\u00fcbingen  T\u00fcbingen Germany"},{"name":"Department for Ophthalmology Institute for Ophthalmic Research, Eberhard Karls University of T\u00fcbingen  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Tang","sequence":"additional","affiliation":[{"name":"Department for Ophthalmology University Eye Clinic, Eberhard Karls University of T\u00fcbingen  T\u00fcbingen Germany"},{"name":"Department for Ophthalmology Institute for Ophthalmic Research, Eberhard Karls University of T\u00fcbingen  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8394-8355","authenticated-orcid":false,"given":"Simon J.","family":"Clark","sequence":"additional","affiliation":[{"name":"Department for Ophthalmology University Eye Clinic, Eberhard Karls University of T\u00fcbingen  T\u00fcbingen Germany"},{"name":"Department for Ophthalmology Institute for Ophthalmic Research, Eberhard Karls University of T\u00fcbingen  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