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Recent evidence indicates that immune system dysregulation could contribute to the development of AMD<\/jats:styled-content>. We hypothesize that defective lysosome\u2010mediated clearance causes accumulation of waste products in the retinal pigmented epithelium (RPE<\/jats:styled-content>), activating the immune system and leading to retinal tissue injury and AMD<\/jats:styled-content>. We have generated unique genetically engineered mice in which lysosome\u2010mediated clearance (both by phagocytosis and autophagy) in RPE<\/jats:styled-content> cells is compromised, causing the development of features of early AMD<\/jats:styled-content>. Our recent data indicate a link between lipocalin\u20102 (LCN<\/jats:styled-content>\u20102) and the inflammatory responses induced in this mouse model. We show that nuclear factor\u2010\u03baB<\/jats:styled-content> (NF\u2010\u03baB<\/jats:styled-content>) and STAT<\/jats:styled-content>\u20101 may function as a complex in our animal model system, together controlling the upregulation of LCN<\/jats:styled-content>\u20102 expression in the retina and stimulating an inflammatory response. This study revealed increased infiltration of LCN<\/jats:styled-content>\u20102\u2010positive neutrophils in the choroid and retina of early AMD<\/jats:styled-content> patients as compared with age\u2010matched controls. Our results demonstrate that, both in our animal model and in human AMD<\/jats:styled-content>, the AKT2\u2013NF\u2010\u03baB\u2013LCN<\/jats:styled-content>\u20102 signalling axis is involved in activating the inflammatory response, making this pathway a potential target for AMD<\/jats:styled-content> treatment. Copyright \u00a9 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.4870","type":"journal-article","created":{"date-parts":[[2016,12,27]],"date-time":"2016-12-27T06:01:06Z","timestamp":1482818466000},"page":"583-588","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Activating the AKT2<\/scp>\u2013nuclear factor\u2010\u03baB<\/scp>\u2013lipocalin\u20102 axis elicits an inflammatory response in age\u2010related macular degeneration"],"prefix":"10.1002","volume":"241","author":[{"given":"Sayan","family":"Ghosh","sequence":"first","affiliation":[{"name":"Department of Ophthalmology The Johns Hopkins University School of Medicine Baltimore MD USA"},{"name":"Department of Physiology University of Calcutta Kolkata WB India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Shang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology The Johns Hopkins University School 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