{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:58:22Z","timestamp":1791928702969,"version":"4.3.4"},"reference-count":52,"publisher":"Association for Research in Vision and Ophthalmology (ARVO)","issue":"1","license":[{"start":{"date-parts":[[2019,1,15]],"date-time":"2019-01-15T00:00:00Z","timestamp":1547510400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Invest. Ophthalmol. Vis. Sci."],"published-print":{"date-parts":[[2019,1,15]]},"DOI":"10.1167\/iovs.18-25878","type":"journal-article","created":{"date-parts":[[2019,1,15]],"date-time":"2019-01-15T11:39:47Z","timestamp":1547552387000},"page":"202","source":"Crossref","is-referenced-by-count":71,"title":["Systemic Levels of Interleukin-6 Correlate With Progression Rate of Geographic Atrophy Secondary to Age-Related Macular Degeneration"],"prefix":"10.1167","volume":"60","author":[{"given":"Marie","family":"Krogh Nielsen","sequence":"first","affiliation":[{"name":"Clinical Eye Research Division, Department of Ophthalmology, Zealand University Hospital, Roskilde, Denmark"},{"name":"Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yousif","family":"Subhi","sequence":"additional","affiliation":[{"name":"Clinical Eye Research Division, Department of Ophthalmology, Zealand University Hospital, Roskilde, Denmark"},{"name":"Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher Rue","family":"Molbech","sequence":"additional","affiliation":[{"name":"Clinical Eye Research Division, Department of Ophthalmology, Zealand University Hospital, Roskilde, Denmark"},{"name":"Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mads Kr\u00fcger","family":"Falk","sequence":"additional","affiliation":[{"name":"Clinical Eye Research Division, Department of Ophthalmology, Zealand University Hospital, Roskilde, Denmark"},{"name":"Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mogens Holst","family":"Nissen","sequence":"additional","affiliation":[{"name":"Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark"},{"name":"Eye Research Unit, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torben Lykke","family":"S\u00f8rensen","sequence":"additional","affiliation":[{"name":"Clinical Eye Research Division, Department of Ophthalmology, Zealand University Hospital, Roskilde, Denmark"},{"name":"Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"27","reference":[{"key":"i1552-5783-60-1-202-b01","doi-asserted-by":"crossref","unstructured":"Al-Zamil WM, Yassin SA. Recent developments in age-related macular degeneration: a review. Clin Interv Aging. 2017; 12: 1313\u20131330.","DOI":"10.2147\/CIA.S143508"},{"key":"i1552-5783-60-1-202-b02","doi-asserted-by":"crossref","unstructured":"Curcio CA, Millican CL. Basal linear deposit and large drusen are specific for early age-related maculopathy. Arch Ophthalmol. 1999; 117: 329\u2013339.","DOI":"10.1001\/archopht.117.3.329"},{"key":"i1552-5783-60-1-202-b03","doi-asserted-by":"crossref","unstructured":"Sarks JP, Sarks SH, Killingsworth MC. Evolution of geographic atrophy of the retinal pigment epithelium. Eye (Lond). 1988; 2: 552\u2013577.","DOI":"10.1038\/eye.1988.106"},{"key":"i1552-5783-60-1-202-b04","doi-asserted-by":"crossref","unstructured":"Jonasson F, Arnarsson A, Eir\u00edksdottir G, et al. Prevalence of age-related macular degeneration in old persons: age, gene\/environment susceptibility Reykjavik study. Ophthalmology. 2011; 118: 825\u2013830.","DOI":"10.1016\/j.ophtha.2010.08.044"},{"key":"i1552-5783-60-1-202-b05","doi-asserted-by":"crossref","unstructured":"Fleckenstein M, Mitchell P, Freund KB, et al. The progression of geographic atrophy secondary to age-related macular degeneration. Ophthalmology. 2018; 125: 369\u2013390.","DOI":"10.1016\/j.ophtha.2017.08.038"},{"key":"i1552-5783-60-1-202-b06","doi-asserted-by":"crossref","unstructured":"Colak E, Ignjatov\u00edc S, Radosavljevic A, \u017doric L. The association of enzymatic and non-enzymatic antioxidant defense in parameters with inflammatory markers in patients with exudative form of age-related macular degeneration. J Clin Biochem Nutr. 2017; 60: 100\u2013107.","DOI":"10.3164\/jcbn.16-30"},{"key":"i1552-5783-60-1-202-b07","doi-asserted-by":"crossref","unstructured":"Haas P, Kubista KE, Krugluger W, Huber J, Binder S. Impact of visceral fat and pro-inflammatory factors on the pathogenesis of age-related macular degeneration. Acta Ophthalmol. 2015; 93: 533\u2013538.","DOI":"10.1111\/aos.12670"},{"key":"i1552-5783-60-1-202-b08","doi-asserted-by":"crossref","unstructured":"Klein R, Myers CE, Cruickshanks KJ, et al. Markers of inflammation, oxidative stress, and endothelial dysfunction and the 20-year cumulative incidence of early age-related macular degeneration: the Beaver Dam Eye Study. JAMA Ophtalmol. 2014; 132: 446\u2013455.","DOI":"10.1001\/jamaophthalmol.2013.7671"},{"key":"i1552-5783-60-1-202-b09","doi-asserted-by":"crossref","unstructured":"Franceschi F, Bonaf\u00e9 M, Valensin S, et al. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci. 2000; 908: 244\u2013254.","DOI":"10.1111\/j.1749-6632.2000.tb06651.x"},{"key":"i1552-5783-60-1-202-b10","doi-asserted-by":"crossref","unstructured":"Frasca D, Blomberg BB. Inflammaging decreases adaptive and innate immune responses in mice and humans. Biogerontology. 2016; 17: 7\u201319.","DOI":"10.1007\/s10522-015-9578-8"},{"key":"i1552-5783-60-1-202-b11","doi-asserted-by":"crossref","unstructured":"Nikolich-Zugich J. Ageing and life-long maintenance of T-cell subsets in the face of latent persistent infections. Nat Rev Immunol. 2008; 8: 512\u2013522.","DOI":"10.1038\/nri2318"},{"key":"i1552-5783-60-1-202-b12","doi-asserted-by":"crossref","unstructured":"Campisi J. Cellular senescence: putting the paradoxes in perspective. Curr Opin Genet Dev. 2011; 21: 107\u2013112.","DOI":"10.1016\/j.gde.2010.10.005"},{"key":"i1552-5783-60-1-202-b13","doi-asserted-by":"crossref","unstructured":"Freund A, Orjalo AV, Desprez PY, Campisi J. Inflammatory networks during cellular senescence: causes and consequences. Trends Mol Med. 2010; 16: 238\u2013246.","DOI":"10.1016\/j.molmed.2010.03.003"},{"key":"i1552-5783-60-1-202-b14","unstructured":"Subhi Y, Singh A, Falk MK, S\u00f8rensen TL. In patients with neovascular age-related macular degeneration, physical activity may influence C-reactive protein levels. Clin Ophthalmol. 2014; 8: 15\u201321."},{"key":"i1552-5783-60-1-202-b15","unstructured":"Subhi Y, S\u00f8rensen TL. Physical activity patterns in patients with early and late age-related macular degeneration. Dan Med J. 2016; 63: A5303."},{"key":"i1552-5783-60-1-202-b16","doi-asserted-by":"crossref","unstructured":"Rifai N, Ridker PM. Proposed cardiovascular risk assessment algorithm using high-sensitivity C-reactive protein and lipid screening. Clin Chem. 2001; 47: 28\u201330.","DOI":"10.1093\/clinchem\/47.1.28"},{"key":"i1552-5783-60-1-202-b17","doi-asserted-by":"crossref","unstructured":"Ferris FL, Wilkinson CP, Bird A, et al. Clinical classification of age-related macular degeneration. Ophthalmology. 2013; 120: 844\u2013851.","DOI":"10.1016\/j.ophtha.2012.10.036"},{"key":"i1552-5783-60-1-202-b18","doi-asserted-by":"crossref","unstructured":"Schmitz-Valckenberg S, Brinkmann CK, Alten F, et al. Semi-automated image processing method for identification and quantification of geographic atrophy in age-related macular degeneration. Invest Ophthalmol Vis Sci. 2011; 52: 7640\u20137646.","DOI":"10.1167\/iovs.11-7457"},{"key":"i1552-5783-60-1-202-b19","doi-asserted-by":"crossref","unstructured":"Faber C, Jehs T, Juel HB, et al. Early and exudative age-related macular degeneration is associated with increased plasma levels of soluble TNF receptor II. Acta Ophthalmol. 2015; 93: 242\u2013247.","DOI":"10.1111\/aos.12581"},{"key":"i1552-5783-60-1-202-b20","doi-asserted-by":"crossref","unstructured":"Bunce C, Patel KV, Xing W, Freemantle N, Dor\u00e9 CJ; Ophthalmic Statistics Group. Ophthalmic statistics note 1: unit of analysis. Br J Ophthalmol. 2014; 98: 408\u2013412.","DOI":"10.1136\/bjophthalmol-2013-304587"},{"key":"i1552-5783-60-1-202-b21","doi-asserted-by":"crossref","unstructured":"Van Woudenbergh GJ, Theofylaktopoulou D, Kujisten A, et al. Adapted dietary inflammatory index and its association with a summary score for low-grade inflammation and markers of glucose metabolism: the Cohort study on Diabetes and Atherosclerosis Maastricht (CODAM) and the Hoorn study. Am J Clin Nutr. 2013; 98: 1533\u20131542.","DOI":"10.3945\/ajcn.112.056333"},{"key":"i1552-5783-60-1-202-b22","unstructured":"Cohen J. Statistical Power Analysis for the Behavioral Sciences. 2nd ed. Hillsdale: Lawrence Erlbaum Associates; 1988."},{"key":"i1552-5783-60-1-202-b23","doi-asserted-by":"crossref","unstructured":"Gregori G, Wang F, Rosenfeld PJ, et al. Spectral domain optical coherence tomography imaging of drusen in nonexudative age-related macular degeneration. Ophthalmology. 2011; 118: 1373\u20131379.","DOI":"10.1016\/j.ophtha.2010.11.013"},{"key":"i1552-5783-60-1-202-b24","doi-asserted-by":"crossref","unstructured":"Yehoshua Z, Wang F, Rosenfeld PJ, Penha FM, Feuer WJ, Gregori G. Natural history of drusen morphology in age-related macular degeneration using spectral domain optical coherence tomography. Ophthalmology. 2011; 118: 2434\u20132441.","DOI":"10.1016\/j.ophtha.2011.05.008"},{"key":"i1552-5783-60-1-202-b25","doi-asserted-by":"crossref","unstructured":"Feuer WJ, Yehoshua Z, Gregori G, et al. Square root transformation of geographic atrophy area measurements to eliminate dependence of growth rates on baseline lesion measurements: a re-analysis of age-related eye disease study. JAMA Ophtalmol. 2013; 131: 110\u2013111.","DOI":"10.1001\/jamaophthalmol.2013.572"},{"key":"i1552-5783-60-1-202-b26","doi-asserted-by":"crossref","unstructured":"De Felice FG, Ferreira ST. Inflammation, defective insulin signaling, and mitochondrial dysfunction as common molecular denominators connecting type 2 diabetes to Alzheimer disease. Diabetes. 2014; 63: 2262\u20132272.","DOI":"10.2337\/db13-1954"},{"key":"i1552-5783-60-1-202-b27","doi-asserted-by":"crossref","unstructured":"Corlier F, Hafzalla G, Faskowitz J, et al. Systemic inflammation as a predictor of brain aging: contributions of physical activity, metabolic risk, and genetic risk. NeuroImage. 2018; 172: 118\u2013129.","DOI":"10.1016\/j.neuroimage.2017.12.027"},{"key":"i1552-5783-60-1-202-b28","doi-asserted-by":"crossref","unstructured":"Touhami S, Beguier F, Augustin S, et al. Chronic exposure to tumor necrosis factor alpha induces retinal pigment epithelium cell dedifferentiation. J Neuroinflammation. 2018; 15: 85.","DOI":"10.1186\/s12974-018-1106-8"},{"key":"i1552-5783-60-1-202-b29","doi-asserted-by":"crossref","unstructured":"Bhutto IA, Baba T, Merges C, Juriasinghani V, McLeods DS, Lutty GA. C-reactive protein and complement factor H in aged human eyes and eyes with age-related macular degeneration. Br J Ophthalmol. 2011; 95: 1323\u20131330.","DOI":"10.1136\/bjo.2010.199216"},{"key":"i1552-5783-60-1-202-b30","doi-asserted-by":"crossref","unstructured":"Johnson PT, Betts KE, Radeke MJ, Hageman GS, Anderson DH, Johnson LV. Individuals homozygous for the age-related macular degeneration risk-conferring variant of complement factor H have elevated levels of CRP in the choroid. Proc Natl Acad Sci U S A. 2006; 103: 17456\u201317461.","DOI":"10.1073\/pnas.0606234103"},{"key":"i1552-5783-60-1-202-b31","doi-asserted-by":"crossref","unstructured":"Taga T, Hibi M, Hirata Y, et al. Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130. Cell. 1989; 58: 573\u2013581.","DOI":"10.1016\/0092-8674(89)90438-8"},{"key":"i1552-5783-60-1-202-b32","doi-asserted-by":"crossref","unstructured":"Rose-John S, Heinrich PC. Soluble receptors for cytokines and growth factors: generation and biological function. Biochem J. 1994; 300: 281\u2013290.","DOI":"10.1042\/bj3000281"},{"key":"i1552-5783-60-1-202-b33","doi-asserted-by":"crossref","unstructured":"Heink S, Yogev N, Garbers C, et al. Trans-presentation of interleukin-6 by dendritic cells is required for priming pathogenic TH17 cells. Nat Immunol. 2017; 18: 74\u201385.","DOI":"10.1038\/ni.3632"},{"key":"i1552-5783-60-1-202-b34","doi-asserted-by":"crossref","unstructured":"Betelli E, Carrier Y, Gao W, et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature. 2006; 441: 235\u2013238.","DOI":"10.1038\/nature04753"},{"key":"i1552-5783-60-1-202-b35","doi-asserted-by":"crossref","unstructured":"Gupta N, Brown KE, Milam AH. Activated microglia in human retinitis pigmentosa, late-onset retinal degeneration, and age-related macular degeneration. Exp Eye Res. 2003; 76: 463\u2013471.","DOI":"10.1016\/S0014-4835(02)00332-9"},{"key":"i1552-5783-60-1-202-b36","doi-asserted-by":"crossref","unstructured":"Combadiere C, Feumi C, Raoul W, et al. CX3CR1-dependent subretinal microglia cell accumulation is associated with cardinal features of age-related macular degeneration. J Clin Invest. 2007; 117: 2920\u20132928.","DOI":"10.1172\/JCI31692"},{"key":"i1552-5783-60-1-202-b37","doi-asserted-by":"crossref","unstructured":"Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation. Nat Rev Immunol. 2008; 8: 958\u2013969.","DOI":"10.1038\/nri2448"},{"key":"i1552-5783-60-1-202-b38","doi-asserted-by":"crossref","unstructured":"Fritsche LG, Loenhardt T, Janssen A, et al. Age-related macular degeneration is associated with an unstable ARMS2 (LOC387715) mRNA. Nature Gen. 2008; 40: 892\u2013896.","DOI":"10.1038\/ng.170"},{"key":"i1552-5783-60-1-202-b39","doi-asserted-by":"crossref","unstructured":"Klein RJ, Zeiss C, Chew EY, et al. Complement factor H polymorphism in age-related macular degeneration. Science. 2005; 308: 385\u2013389.","DOI":"10.1126\/science.1109557"},{"key":"i1552-5783-60-1-202-b40","doi-asserted-by":"crossref","unstructured":"Fritsche LG, Chen W, Schu M, et al. Seven new loci associated with age-related macular degeneration. Nat Genet. 2013; 45: 433\u2013439.","DOI":"10.1038\/ng.2578"},{"key":"i1552-5783-60-1-202-b41","doi-asserted-by":"crossref","unstructured":"Seddon JM, Francis PJ, George S, Schultz DW, Rosner B, Klein ML. Association of CFH Y402H and LOC387715 A69S with progression of age-related macular degeneration. JAMA. 2007; 297: 1793\u20131800.","DOI":"10.1001\/jama.297.16.1793"},{"key":"i1552-5783-60-1-202-b42","unstructured":"Yasuma TR, Nakamura M, Nishiguchi KM, et al. Elevated C-reactive protein levels and ARMS2\/HTRA1 gene variants in subjects without age-related macular degeneration. Mol Vis. 2010; 16: 2923\u20132930."},{"key":"i1552-5783-60-1-202-b43","doi-asserted-by":"crossref","unstructured":"Wu R, Liu X, Yin J, et al. IL-6 blockade ameliorates diabetic nephropathy via inhibiting inflammasome in mice. Metabolism. 2018; 83: 18\u201324.","DOI":"10.1016\/j.metabol.2018.01.002"},{"key":"i1552-5783-60-1-202-b44","doi-asserted-by":"crossref","unstructured":"Powell N, Lo JW, Biancheri P, et al. Interleukin 6 increases production of cytokines by colonic innate lymphoid cells in mice and patients with chronic intestinal inflammation. Gastroenterology. 2015; 149: 456\u2013467.","DOI":"10.1053\/j.gastro.2015.04.017"},{"key":"i1552-5783-60-1-202-b45","doi-asserted-by":"crossref","unstructured":"Zhang S, Yu N, Zhang R, Zhang S, Wu J. Interleukin-17A induces IL-1\u00df secretion from RPE cells via the NLRP3 inflammasome. Invest Ophthalmol Vis Sci. 2016; 57: 312\u2013319.","DOI":"10.1167\/iovs.15-17578"},{"key":"i1552-5783-60-1-202-b46","doi-asserted-by":"crossref","unstructured":"Charo IF, Ransohoff RM. The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med. 2006; 354: 610\u2013621.","DOI":"10.1056\/NEJMra052723"},{"key":"i1552-5783-60-1-202-b47","doi-asserted-by":"crossref","unstructured":"Goczalik I, Ulbricht E, Hollborn M, et al. Expression of CXCL8, CXCR1, and CXCR2 in neurons and glial cells of the human and rabbit retina. Invest Ophthalmol Vis Sci. 2008; 49: 4578\u20134589.","DOI":"10.1167\/iovs.08-1887"},{"key":"i1552-5783-60-1-202-b48","doi-asserted-by":"crossref","unstructured":"Juel HB, Faber C, Udsen MS, Folkersen L, Nissen MH. Chemokine expression in retinal pigment epithelial ARPE-19 cells in response to coculture with activated T cells. Invest Ophthalmol Vis Sci. 2012; 53: 8472\u20138480.","DOI":"10.1167\/iovs.12-9963"},{"key":"i1552-5783-60-1-202-b49","doi-asserted-by":"crossref","unstructured":"Liu YJ, Guo DW, Tian L, et al. Peripheral T cells derived from Alzheimer's disease patients overexpress CXCR2 contributing to its transendothelial migration, which is microglial TNF-alpha-dependent. Neurobiol Aging. 2010; 31: 175\u2013188.","DOI":"10.1016\/j.neurobiolaging.2008.03.024"},{"key":"i1552-5783-60-1-202-b50","doi-asserted-by":"crossref","unstructured":"Ghanemi A, St-Amand J. Interleukin-6 as a \u201cmetabolic hormone\u201d. Cytokine. 2018; 112: 132\u2013136.","DOI":"10.1016\/j.cyto.2018.06.034"},{"key":"i1552-5783-60-1-202-b51","doi-asserted-by":"crossref","unstructured":"Jostock T, M\u00fcllberg J, Ozbek S, et al. Soluble gp130 is the natural inhibitor of soluble interleukin-6 receptor transsignaling responses. Eur J Biochem. 2001; 268: 160\u2013167.","DOI":"10.1046\/j.1432-1327.2001.01867.x"},{"key":"i1552-5783-60-1-202-b52","doi-asserted-by":"crossref","unstructured":"Narazaki M, Yasukawa K, Saito T, et al. Soluble forms of the interleukin-6 signal-transducing receptor component gp130 in human serum possessing a potential to inhibit signals through membrane-anchored gp130. Blood. 1993; 82: 1120\u20131126.","DOI":"10.1182\/blood.V82.4.1120.1120"}],"container-title":["Investigative Opthalmology & Visual Science"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/iovs.arvojournals.org\/article.aspx?articleid=2720952","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:31:04Z","timestamp":1791927064000},"score":1,"resource":{"primary":{"URL":"http:\/\/iovs.arvojournals.org\/article.aspx?doi=10.1167\/iovs.18-25878"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,15]]},"references-count":52,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,1,2]]}},"URL":"https:\/\/doi.org\/10.1167\/iovs.18-25878","relation":{},"ISSN":["1552-5783"],"issn-type":[{"value":"1552-5783","type":"print"}],"subject":[],"published":{"date-parts":[[2019,1,15]]}}}