{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T15:10:00Z","timestamp":1792422600397,"version":"4.5.0"},"reference-count":211,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,23]],"date-time":"2023-06-23T00:00:00Z","timestamp":1687478400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute for Health Research (NIHR)"},{"name":"Wessex Medical Research (WMR)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Landmark genetic studies have revealed the effect of complement biology and its regulation of the pathogenesis of age-related macular degeneration (AMD). Limited phase 3 clinical trial data showing a benefit of complement inhibition in AMD raises the prospect of more complex mediators at play. Substantial evidence supports the role of para-inflammation in maintaining homeostasis in the retina and choroid. With increasing age, a decline in immune system regulation, known as immunosenescence, has been shown to alter the equilibrium maintained by para-inflammation. The altered equilibrium results in chronic, sterile inflammation with aging, termed \u2018inflammaging\u2019, including in the retina and choroid. The chronic inflammatory state in AMD is complex, with contributions from cells of the innate and adaptive branches of the immune system, sometimes with overlapping features, and the interaction of their secretory products with retinal cells such as microglia and retinal pigment epithelium (RPE), extracellular matrix and choroidal vascular endothelial cells. In this review, the chronic inflammatory state in AMD will be explored by immune cell type, with a discussion of factors that will need to be overcome in the development of curative therapies.<\/jats:p>","DOI":"10.3390\/cells12131708","type":"journal-article","created":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T02:23:09Z","timestamp":1687746189000},"page":"1708","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Beyond the Complement Cascade: Insights into Systemic Immunosenescence and Inflammaging in Age-Related Macular Degeneration and Current Barriers to Treatment"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8153-8002","authenticated-orcid":false,"given":"Adnan H.","family":"Khan","sequence":"first","affiliation":[{"name":"Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO17 1BJ, UK"},{"name":"Southampton Eye Unit, University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itay","family":"Chowers","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel"},{"name":"Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91121, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5541-4305","authenticated-orcid":false,"given":"Andrew J.","family":"Lotery","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO17 1BJ, UK"},{"name":"Southampton Eye Unit, University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e106","DOI":"10.1016\/S2214-109X(13)70145-1","article-title":"Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: A systematic review and meta-analysis","volume":"2","author":"Wong","year":"2014","journal-title":"Lancet Glob. 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