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Olink proteomic analysis and single-cell RNA sequencing combined with knockout studies demonstrated the involvement of C-C chemokine receptor 5 (CCR5) in NK cell recruitment and extravasation at the CNV sites of mice. Depletion of NK cells or inhibition of activating receptor NK group 2, member D (NKG2D) inhibited the formation of neutrophil extracellular traps, increased vascular leakage, and exacerbated pathological angiogenesis, indicating that NK cells restrain pathogenesis in this mouse model. Age is the strongest risk factor for AMD, and we show that NK cells from aged human donors exhibited a less cytotoxic phenotype. NK cells from old mice exhibited compromised protective effects in the CNV mouse model. In addition, interleukin-2 complex\u2013mediated expansion of NK cells improved CNV formation in mice. Collectively, our study highlights NK cells as a potential therapeutic target for patients with nvAMD.<\/jats:p>","DOI":"10.1126\/scitranslmed.adi6626","type":"journal-article","created":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T13:58:31Z","timestamp":1723643911000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":22,"title":["Natural killer cells promote neutrophil extracellular traps and restrain macular degeneration in mice"],"prefix":"10.1126","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-1233-8674","authenticated-orcid":true,"given":"Xue","family":"Dong","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Laboratory of Molecular Ophthalmology and Tianjin Key Laboratory of Ocular Trauma, Ministry of Education International Joint Laboratory of Ocular Diseases, Tianjin Institute of Eye Health and Eye Diseases, China-UK \u201cBelt and Road\u201d Ophthalmology Joint Laboratory, 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