{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T15:19:06Z","timestamp":1783523946249,"version":"3.55.0"},"reference-count":88,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T00:00:00Z","timestamp":1705968000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Previous studies have explored the associations between circulating inflammatory cytokines and blinding eye diseases, including glaucoma, cataract and macular degeneration. However, the causality of these associations remains controversial. This study employs a bidirectional Mendelian randomization (MR) study to investigate the causal relationships between 41 circulating inflammatory cytokines and these blinding eye diseases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Summary data for glaucoma, cataract, macular degeneration and 41 circulating inflammatory cytokines were publicly available. The inverse variance weighted (IVW) method was employed as the main analysis method. Additionally, various sensitivity tests, including MR\u2013Egger regression, weighted median, weight mode, Cochran\u2019s Q test, MR pleiotropy Residual Sum and Outlier test, and leave-one-out test, were conducted to evaluate sensitivity and stability of results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The IVW analysis identified six circulating inflammatory cytokines causally associated with the risk of blinding eye diseases: Monokine induced by interferon-gamma (MIG) for glaucoma, interleukin-1 receptor antagonist (IL-1ra), IL-6, IL-10, and platelet derived growth factor BB (PDGFbb) for cataract, and MIG and hepatocyte growth factor (HGF) for macular degeneration. However, it is noteworthy that none of these associations remained significant after Bonferroni correction (<jats:italic>p<\/jats:italic> &amp;lt;\u20090.0004). Reverse MR analyses indicated that cataract may lead to a decrease in vascular endothelial growth factor (VEGF) levels (OR: 3.326\u2009\u00d7\u200910<jats:sup>\u221204<\/jats:sup>, 95% CI: 5.198\u2009\u00d7\u200910<jats:sup>\u221207<\/jats:sup> \u2212\u20092.129\u2009\u00d7\u200910<jats:sup>\u221201<\/jats:sup>, <jats:italic>p<\/jats:italic> =\u20090.0151).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study highlights the potential roles of specific inflammatory cytokines in the development of glaucoma, cataract and macular degeneration. Moreover, it suggests that VEGF is likely to be involved in cataract development downstream. These findings offer insights for early prevention and novel therapeutic strategies for these blinding eye diseases.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnagi.2024.1324651","type":"journal-article","created":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T04:17:03Z","timestamp":1705983423000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Causal associations between circulating inflammatory cytokines and blinding eye diseases: a bidirectional Mendelian randomization analysis"],"prefix":"10.3389","volume":"16","author":[{"given":"Menghao","family":"Teng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiachen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochen","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomin","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,1,23]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1811","DOI":"10.1097\/iae.0000000000000157","article-title":"Profile of intraocular immune mediators in patients with age-related macular degeneration and the effect of intravitreal bevacizumab injection","volume":"34","author":"Agawa","year":"2014","journal-title":"Retina"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.ajhg.2016.11.007","article-title":"Genome-wide association study identifies 27 loci influencing concentrations of circulating cytokines and growth factors","volume":"100","author":"Ahola-Olli","year":"2017","journal-title":"Am. J. Hum. Genet."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.exer.2018.11.005","article-title":"All roads lead to glaucoma: induced retinal injury cascades contribute to a common neurodegenerative outcome","volume":"183","author":"Alqawlaq","year":"2019","journal-title":"Exp. Eye Res."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"7100","DOI":"10.1167\/iovs.15-17660","article-title":"Profiling of cytokines secreted by conventional aqueous outflow pathway endothelial cells activated in vitro and ex vivo with laser irradiation","volume":"56","author":"Alvarado","year":"2015","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1038\/nri3459","article-title":"Immunology of age-related macular degeneration","volume":"13","author":"Ambati","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/aos.12452","article-title":"Development of gene therapy for treatment of age-related macular degeneration","volume":"92","author":"Askou","year":"2014","journal-title":"Acta Ophthalmol."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"100916","DOI":"10.1016\/j.preteyeres.2020.100916","article-title":"Inflammation in Glaucoma: from the back to the front of the eye, and beyond","volume":"83","author":"Baudouin","year":"2021","journal-title":"Prog. Retin. Eye Res."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1093\/ije\/dyv080","article-title":"Mendelian randomization with invalid instruments: effect estimation and bias detection through egger regression","volume":"44","author":"Bowden","year":"2015","journal-title":"Int. J. Epidemiol."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1002\/gepi.21965","article-title":"Consistent estimation in Mendelian randomization with some invalid instruments using a weighted median estimator","volume":"40","author":"Bowden","year":"","journal-title":"Genet. Epidemiol."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"dyw220","DOI":"10.1093\/ije\/dyw220","article-title":"Assessing the suitability of summary data for two-sample Mendelian randomization analyses using MR-egger regression: the role of the I2 statistic","volume":"45","author":"Bowden","year":"","journal-title":"Int. J. Epidemiol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.1093\/ije\/dyt179","article-title":"Calculating statistical power in Mendelian randomization studies","volume":"42","author":"Brion","year":"2013","journal-title":"Int. J. Epidemiol."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1093\/ije\/dyu005","article-title":"Sample size and power calculations in Mendelian randomization with a single instrumental variable and a binary outcome","volume":"43","author":"Burgess","year":"2014","journal-title":"Int. J. Epidemiol."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1880","DOI":"10.1002\/sim.6835","article-title":"Combining information on multiple instrumental variables in Mendelian randomization: comparison of allele score and summarized data methods","volume":"35","author":"Burgess","year":"2016","journal-title":"Stat. Med."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"e768","DOI":"10.1111\/aos.14374","article-title":"Tear and aqueous humour cytokine profile in primary open-angle glaucoma","volume":"98","author":"Burgos-Blasco","year":"2020","journal-title":"Acta Ophthalmol."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"e109647","DOI":"10.1371\/journal.pone.0109647","article-title":"Discrepant expression of cytokines in inflammation-and age-related cataract patients","volume":"9","author":"Chen","year":"2014","journal-title":"PLoS One"},{"key":"ref16","first-page":"1005","article-title":"Increased levels of IL-6, sIL-6R, and sgp130 in the aqueous humor and serum of patients with diabetic retinopathy","volume":"22","author":"Chen","year":"2016","journal-title":"Mol. Vis."},{"key":"ref17","first-page":"431","article-title":"Expression profile of inflammatory cytokines in aqueous from glaucomatous eyes","volume":"18","author":"Chua","year":"2012","journal-title":"Mol. Vis."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1101\/cshperspect.a017236","article-title":"Clinical characteristics and current treatment of glaucoma","volume":"4","author":"Cohen","year":"2014","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"12088","DOI":"10.1523\/jneurosci.1273-15.2015","article-title":"Soluble tumor necrosis factor alpha promotes retinal ganglion cell death in Glaucoma via calcium-permeable AMPA receptor activation","volume":"35","author":"Cueva Vargas","year":"2015","journal-title":"J. Neurosci."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"3167","DOI":"10.26355\/eurrev_201904_17674","article-title":"Correlation between MMP-2 gene polymorphism and cataract susceptibility","volume":"23","author":"Dong","year":"2019","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1080\/02713683.2020.1715445","article-title":"Cytokine and chemokine concentration in the tear of patients with age-related cataract","volume":"45","author":"Engelbrecht","year":"2020","journal-title":"Curr. Eye Res."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1038\/s41572-021-00265-2","article-title":"Age-related macular degeneration","volume":"7","author":"Fleckenstein","year":"2021","journal-title":"Nat. Rev. Dis. Primers."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"101697","DOI":"10.1016\/j.arr.2022.101697","article-title":"The hormetic and hermetic role of IL-6","volume":"80","author":"Forcina","year":"2022","journal-title":"Ageing Res. Rev."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"5","DOI":"10.3390\/md18050239","article-title":"Clinical applications of Astaxanthin in the treatment of ocular diseases: emerging insights","volume":"18","author":"Giannaccare","year":"2020","journal-title":"Mar. Drugs"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1717","DOI":"10.1093\/ije\/dyx028","article-title":"Two-sample Mendelian randomization: avoiding the downsides of a powerful, widely applicable but potentially fallible technique","volume":"45","author":"Hartwig","year":"2016","journal-title":"Int. J. Epidemiol."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1038\/s41433-020-0806-3","article-title":"Global and regional prevalence of age-related cataract: a comprehensive systematic review and meta-analysis","volume":"34","author":"Hashemi","year":"2020","journal-title":"Eye"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1006\/bbrc.1998.9087","article-title":"Retinal pigment epithelial cells secrete and respond to hepatocyte growth factor","volume":"249","author":"He","year":"1998","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"421","DOI":"10.2337\/dc08-1161","article-title":"Elevated levels of the anti-inflammatory interleukin-1 receptor antagonist precede the onset of type 2 diabetes: the Whitehall II study","volume":"32","author":"Herder","year":"2009","journal-title":"Diabetes Care"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1038\/nature21363","article-title":"Inflammation, metaflammation and immunometabolic disorders","volume":"542","author":"Hotamisligil","year":"2017","journal-title":"Nature"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1097\/00061198-200106000-00002","article-title":"Hepatocyte growth factor is increased in the aqueous humor of glaucomatous eyes","volume":"10","author":"Hu","year":"2001","journal-title":"J. Glaucoma"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1038\/s41419-021-04489-8","article-title":"Autophagy facilitates age-related cell apoptosis-a new insight from senile cataract","volume":"13","author":"Huang","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"2277","DOI":"10.3892\/mmr.2018.9188","article-title":"Pyroptosis, a novel mechanism implicated in cataracts","volume":"18","author":"Jin","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"244","DOI":"10.3341\/kjo.2007.21.4.244","article-title":"Role of HGF\/c-met in serum-starved ARPE-19 cells","volume":"21","author":"Jun","year":"2007","journal-title":"Korean J. Ophthalmol."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"615","DOI":"10.3233\/jad-2011-101908","article-title":"Age-related macular degeneration (AMD): Alzheimer's disease in the eye?","volume":"24","author":"Kaarniranta","year":"2011","journal-title":"J. Alzheimers Dis."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.mam.2014.05.001","article-title":"HMGB1 in health and disease","volume":"40","author":"Kang","year":"2014","journal-title":"Mol. Asp. Med."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1016\/j.mcna.2021.01.004","article-title":"Glaucoma","volume":"105","author":"Kang","year":"2021","journal-title":"Med. Clin. North Am."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1111\/jpi.12016","article-title":"Neuroprotective effect of melatonin against hypoxia-induced retinal ganglion cell death in neonatal rats","volume":"54","author":"Kaur","year":"2013","journal-title":"J. Pineal Res."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1016\/j.ophtha.2009.10.007","article-title":"The prevalence of age-related macular degeneration in Asians: a systematic review and meta-analysis","volume":"117","author":"Kawasaki","year":"2010","journal-title":"Ophthalmology"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.jdermsci.2016.02.003","article-title":"Up-regulation of receptor antagonist interleukin-1 family members in psoriasis and their regulation by pro-inflammatory cytokines","volume":"82","author":"Kim","year":"2016","journal-title":"J. Dermatol. Sci."},{"key":"ref40","first-page":"737","article-title":"Differential regulation of microRNA-146a and microRNA-146b-5p in human retinal pigment epithelial cells by interleukin-1\u03b2, tumor necrosis factor-\u03b1, and interferon-\u03b3","volume":"19","author":"Kutty","year":"2013","journal-title":"Mol. Vis."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.exer.2013.04.008","article-title":"The dark phase intraocular pressure elevation and retinal ganglion cell degeneration in a rat model of experimental glaucoma","volume":"112","author":"Kwong","year":"2013","journal-title":"Exp. Eye Res."},{"key":"ref42","first-page":"149","article-title":"Hepatocyte growth factor receptor in human RPE cells: implications in proliferative vitreoretinopathy","volume":"40","author":"Lashkari","year":"1999","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.maturitas.2022.05.002","article-title":"Glaucoma -risk factors and current challenges in the diagnosis of a leading cause of visual impairment","volume":"163","author":"Lee","year":"2022","journal-title":"Maturitas"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"e3000133","DOI":"10.1371\/journal.pbio.3000133","article-title":"Lens differentiation is controlled by the balance between PDGF and FGF signaling","volume":"17","author":"Li","year":"2019","journal-title":"PLoS Biol."},{"key":"ref45","first-page":"727","article-title":"Hepatocyte growth factor and hepatocyte growth factor receptor in the lacrimal gland, tears, and cornea","volume":"37","author":"Li","year":"1996","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"3","DOI":"10.3390\/ijms21030899","article-title":"NOD-like receptors in the eye: uncovering its role in diabetic retinopathy","volume":"21","author":"Lim","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1016\/j.bbrc.2005.09.182","article-title":"Induction of IL-6 expression by mechanical stress in the trabecular meshwork","volume":"337","author":"Liton","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1016\/s0140-6736(17)30544-5","article-title":"Cataracts","volume":"390","author":"Liu","year":"2017","journal-title":"Lancet"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"314","DOI":"10.3760\/cma.j.issn.0412-4081.2017.04.016","article-title":"Correlation between Alzheimer disease and cataract","volume":"53","author":"Liu","year":"2017","journal-title":"Zhonghua Yan Ke Za Zhi"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1093\/ecco-jcc\/jjab191","article-title":"Depression and inflammatory bowel disease: a bidirectional two-sample Mendelian randomization study","volume":"16","author":"Luo","year":"2022","journal-title":"J. Crohns Colitis"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1093\/gerona\/61.6.575","article-title":"Interleukin-6 in aging and chronic disease: a magnificent pathway","volume":"61","author":"Maggio","year":"2006","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/life13010077","article-title":"Potential properties of natural nutraceuticals and antioxidants in age-related eye disorders","volume":"13","author":"Maiuolo","year":"2022","journal-title":"Life"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"101954","DOI":"10.1016\/j.arr.2023.101954","article-title":"The central role of the NLRP3 inflammasome pathway in the pathogenesis of age-related diseases in the eye and the brain","volume":"88","author":"Maran","year":"2023","journal-title":"Ageing Res. Rev."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"12","DOI":"10.3390\/jcm10122538","article-title":"Management of Cataract in patients with age-related macular degeneration","volume":"10","author":"Mehta","year":"2021","journal-title":"J. Clin. Med."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1159\/000490153","article-title":"Aqueous humor levels of cytokines in patients with age-related macular degeneration","volume":"241","author":"Mimura","year":"2019","journal-title":"Ophthalmologica"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"9682","DOI":"10.3390\/ijms23179682","article-title":"Ubiquitin specific protease USP48 destabilizes NF-\u03baB\/p65 in retinal pigment epithelium cells","volume":"23","author":"Mirra","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"ref57","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3109\/09273948.2014.949779","article-title":"Levels of selected aqueous humor mediators (IL-10, IL-17, CCL2, VEGF, FasL) in diabetic cataract","volume":"24","author":"Mitrovi\u0107","year":"2016","journal-title":"Ocul. Immunol. Inflamm."},{"key":"ref58","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1038\/nri2448","article-title":"Exploring the full spectrum of macrophage activation","volume":"8","author":"Mosser","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1080\/02713680600629797","article-title":"Protective effect of hepatocyte growth factor against degeneration of the retinal pigment epithelium and photoreceptor in sodium iodate-injected rats","volume":"31","author":"Ohtaka","year":"2006","journal-title":"Curr. Eye Res."},{"key":"ref60","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1007\/s10875-012-9766-0","article-title":"Increased T-cell activation and Th1 cytokine concentrations prior to the diagnosis of B-cell lymphoma in HIV infected patients","volume":"33","author":"Ouedraogo","year":"2013","journal-title":"J. Clin. Immunol."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1038\/s41598-022-05183-1","article-title":"Essential function of adaptor protein Nck1 in platelet-derived growth factor receptor signaling in human lens epithelial cells","volume":"12","author":"Paensuwan","year":"2022","journal-title":"Sci. Rep."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"e40065","DOI":"10.1371\/journal.pone.0040065","article-title":"Etanercept, a widely used inhibitor of tumor necrosis factor-\u03b1 (TNF-\u03b1), prevents retinal ganglion cell loss in a rat model of glaucoma","volume":"7","author":"Roh","year":"2012","journal-title":"PLoS One"},{"key":"ref63","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1189\/jlb.1105674","article-title":"Interleukin-6 biology is coordinated by membrane-bound and soluble receptors: role in inflammation and cancer","volume":"80","author":"Rose-John","year":"2006","journal-title":"J. Leukoc. Biol."},{"key":"ref64","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/j.cytogfr.2010.11.001","article-title":"IL-10 family of cytokines","volume":"21","author":"Sabat","year":"2010","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref65","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1007\/s00417-016-3313-2","article-title":"Intraocular cytokines imbalance in congenital cataract and its impact on posterior capsule opacification","volume":"254","author":"Sauer","year":"2016","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref66","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/nrrheum.2015.167","article-title":"Type I\/II cytokines, JAKs, and new strategies for treating autoimmune diseases","volume":"12","author":"Schwartz","year":"2016","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref67","doi-asserted-by":"publisher","first-page":"107598","DOI":"10.1016\/j.intimp.2021.107598","article-title":"MCP-1: function, regulation, and involvement in disease","volume":"101","author":"Singh","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"ref68","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1093\/ije\/dyh132","article-title":"Mendelian randomization: prospects, potentials, and limitations","volume":"33","author":"Smith","year":"2004","journal-title":"Int. J. Epidemiol."},{"key":"ref69","doi-asserted-by":"publisher","first-page":"e0203337","DOI":"10.1371\/journal.pone.0203337","article-title":"Cytokine profiles in the aqueous humor and serum of patients with dry and treated wet age-related macular degeneration","volume":"13","author":"Spindler","year":"2018","journal-title":"PLoS One"},{"key":"ref70","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1152\/physrev.00021.2004","article-title":"The retinal pigment epithelium in visual function","volume":"85","author":"Strauss","year":"2005","journal-title":"Physiol. Rev."},{"key":"ref71","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1016\/j.cell.2010.01.022","article-title":"Pattern recognition receptors and inflammation","volume":"140","author":"Takeuchi","year":"2010","journal-title":"Cell"},{"key":"ref72","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1016\/j.cyto.2014.12.027","article-title":"Th1\/Th2\/Th17\/Treg cytokine imbalance in systemic lupus erythematosus (SLE) patients: correlation with disease activity","volume":"72","author":"Talaat","year":"2015","journal-title":"Cytokine"},{"key":"ref73","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1111\/aos.13899","article-title":"Intraocular cytokine profile and autoimmune reactions in retinitis pigmentosa, age-related macular degeneration, glaucoma and cataract","volume":"97","author":"Ten Berge","year":"2019","journal-title":"Acta Ophthalmol."},{"key":"ref74","doi-asserted-by":"publisher","first-page":"2081","DOI":"10.1016\/j.ophtha.2014.05.013","article-title":"Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis","volume":"121","author":"Tham","year":"2014","journal-title":"Ophthalmology"},{"key":"ref75","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.ctrv.2017.11.007","article-title":"CXCL9, CXCL10, CXCL11\/CXCR3 axis for immune activation -a target for novel cancer therapy","volume":"63","author":"Tokunaga","year":"2018","journal-title":"Cancer Treat. Rev."},{"key":"ref76","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1038\/s41588-018-0099-7","article-title":"Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases","volume":"50","author":"Verbanck","year":"2018","journal-title":"Nat. Genet."},{"key":"ref77","doi-asserted-by":"publisher","first-page":"2404","DOI":"10.1016\/j.clnu.2023.10.008","article-title":"The inflammatory potential of diet is associated with the risk of age-related eye diseases","volume":"42","author":"Vergroesen","year":"2023","journal-title":"Clin. Nutr."},{"key":"ref78","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.cyto.2018.10.019","article-title":"Diverse effects of platelet-derived growth factor-BB on cell signaling pathways","volume":"113","author":"Wang","year":"2019","journal-title":"Cytokine"},{"key":"ref79","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1007\/s11926-021-00984-1","article-title":"A review of complement activation in SLE","volume":"23","author":"Weinstein","year":"2021","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref80","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1016\/j.preteyeres.2009.06.001","article-title":"Para-inflammation in the aging retina","volume":"28","author":"Xu","year":"2009","journal-title":"Prog. Retin. Eye Res."},{"key":"ref81","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1186\/s12886-020-01661-0","article-title":"Plasma lipid levels and risk of primary open angle glaucoma: a genetic study using Mendelian randomization","volume":"20","author":"Xu","year":"2020","journal-title":"BMC Ophthalmol."},{"key":"ref82","doi-asserted-by":"publisher","first-page":"808832","DOI":"10.3389\/fimmu.2022.808832","article-title":"No genetic causal association between periodontitis and arthritis: a bidirectional two-sample Mendelian randomization analysis","volume":"13","author":"Yin","year":"2022","journal-title":"Front. Immunol."},{"key":"ref83","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1002\/1098-1136(200010)32:1<42::AID-GLIA40>3.0.CO;2-3","article-title":"Tumor necrosis factor-alpha: a potentially neurodestructive cytokine produced by glia in the human glaucomatous optic nerve head","volume":"32","author":"Yuan","year":"2000","journal-title":"Glia"},{"key":"ref84","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1038\/s41598-021-04515-x","article-title":"Metabolic and lifestyle factors in relation to senile cataract: a Mendelian randomization study","volume":"12","author":"Yuan","year":"2022","journal-title":"Sci. Rep."},{"key":"ref85","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1208\/s12249-020-01774-1","article-title":"Intractable ocular diseases and treatment Progress","volume":"21","author":"Zhang","year":"2020","journal-title":"AAPS PharmSciTech"},{"key":"ref86","doi-asserted-by":"publisher","first-page":"2648267","DOI":"10.1155\/2019\/2648267","article-title":"A systematic review and Meta-analysis of clinical outcomes of intravitreal anti-VEGF agent treatment immediately after cataract surgery for patients with diabetic retinopathy","volume":"2019","author":"Zhao","year":"2019","journal-title":"J. Ophthalmol."},{"key":"ref87","doi-asserted-by":"publisher","first-page":"1390","DOI":"10.1016\/j.joca.2022.06.006","article-title":"Osteoarthritis & stroke: a bidirectional mendelian randomization study","volume":"30","author":"Zhao","year":"2022","journal-title":"Osteoarthr. Cartil."},{"key":"ref88","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1093\/ije\/dyz121","article-title":"Education and lung cancer: a Mendelian randomization study","volume":"48","author":"Zhou","year":"2019","journal-title":"Int. J. Epidemiol."}],"container-title":["Frontiers in Aging Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2024.1324651\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T04:17:12Z","timestamp":1705983432000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2024.1324651\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,23]]},"references-count":88,"alternative-id":["10.3389\/fnagi.2024.1324651"],"URL":"https:\/\/doi.org\/10.3389\/fnagi.2024.1324651","relation":{},"ISSN":["1663-4365"],"issn-type":[{"value":"1663-4365","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,23]]},"article-number":"1324651"}}