{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T07:45:31Z","timestamp":1793259931951,"version":"4.5.0"},"reference-count":51,"publisher":"Association for Research in Vision and Ophthalmology (ARVO)","issue":"6","license":[{"start":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T00:00:00Z","timestamp":1748995200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Invest. Ophthalmol. Vis. Sci."],"published-print":{"date-parts":[[2025,6,4]]},"DOI":"10.1167\/iovs.66.6.13","type":"journal-article","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T11:30:39Z","timestamp":1749036639000},"page":"13","source":"Crossref","is-referenced-by-count":9,"title":["Activation of Sympathetic Nervous System Drives Dry Eye Onset Via Norepinephrine-\u03b22-Adrenergic Receptor Signaling in Mice"],"prefix":"10.1167","volume":"66","author":[{"given":"Mingli","family":"Qu","sequence":"first","affiliation":[{"name":"Eye Institute of Shandong First Medical University, Qingdao, People's Republic of China"},{"name":"State Key Laboratory Cultivation Base, Shandong Key Laboratory of Eye Diseases, Qingdao, People's Republic of China"},{"name":"School of Ophthalmology, Shandong First Medical University, Qingdao, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofei","family":"Bai","sequence":"additional","affiliation":[{"name":"Eye Institute of Shandong First Medical University, Qingdao, People's Republic of China"},{"name":"State Key Laboratory Cultivation Base, Shandong Key Laboratory of Eye Diseases, Qingdao, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Eye Institute of Shandong First Medical University, Qingdao, People's Republic of China"},{"name":"State Key Laboratory Cultivation Base, Shandong Key Laboratory of Eye Diseases, Qingdao, People's Republic of China"},{"name":"School of Ophthalmology, Shandong First Medical University, Qingdao, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyi","family":"Wu","sequence":"additional","affiliation":[{"name":"Eye Institute of Shandong First Medical University, Qingdao, People's Republic of China"},{"name":"State Key Laboratory Cultivation Base, Shandong Key Laboratory of Eye Diseases, Qingdao, People's Republic of China"},{"name":"School of Ophthalmology, Shandong First Medical University, Qingdao, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wan","sequence":"additional","affiliation":[{"name":"Eye Institute of Shandong First Medical University, Qingdao, People's Republic of China"},{"name":"State Key Laboratory Cultivation Base, Shandong Key Laboratory of Eye Diseases, Qingdao, People's Republic of China"},{"name":"School of Ophthalmology, Shandong First Medical University, Qingdao, People's Republic of China"},{"name":"Qingdao Eye Hospital of Shandong First Medical University, Qingdao, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Li","sequence":"additional","affiliation":[{"name":"Eye Institute of Shandong First Medical University, Qingdao, People's Republic of China"},{"name":"State Key Laboratory Cultivation Base, Shandong Key Laboratory of Eye Diseases, Qingdao, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qun","family":"Wang","sequence":"additional","affiliation":[{"name":"Eye Institute of Shandong First Medical University, Qingdao, People's Republic of China"},{"name":"State Key Laboratory Cultivation Base, Shandong Key Laboratory of Eye Diseases, Qingdao, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Cong","sequence":"additional","affiliation":[{"name":"Eye Institute of Shandong First Medical University, Qingdao, People's Republic of China"},{"name":"State Key Laboratory Cultivation Base, Shandong Key Laboratory of Eye Diseases, Qingdao, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benxiang","family":"Qi","sequence":"additional","affiliation":[{"name":"Eye Institute of Shandong First Medical University, Qingdao, People's Republic of China"},{"name":"State Key Laboratory Cultivation Base, Shandong Key Laboratory of Eye Diseases, Qingdao, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingjun","family":"Zhou","sequence":"additional","affiliation":[{"name":"Eye Institute of Shandong First Medical University, Qingdao, People's Republic of China"},{"name":"State Key Laboratory Cultivation Base, Shandong Key Laboratory of Eye Diseases, Qingdao, People's Republic of China"},{"name":"School of Ophthalmology, Shandong First Medical University, Qingdao, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"27","reference":[{"issue":"3","key":"bib1","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1016\/j.jtos.2017.05.008","article-title":"TFOS DEWS II definition and classification report","volume":"15","author":"Craig","year":"2017","journal-title":"Ocul Surf"},{"issue":"23","key":"bib2","doi-asserted-by":"publisher","first-page":"2212","DOI":"10.1056\/NEJMra1407936","article-title":"Dry eye","volume":"378","author":"Clayton","year":"2018","journal-title":"N Engl J Med"},{"issue":"3","key":"bib3","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1016\/j.jtos.2017.05.002","article-title":"TFOS DEWS II pain and sensation report","volume":"15","author":"Belmonte","year":"2017","journal-title":"Ocul Surf"},{"issue":"3","key":"bib4","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1016\/j.jtos.2017.05.003","article-title":"TFOS DEWS II epidemiology report","volume":"15","author":"Stapleton","year":"2017","journal-title":"Ocul Surf"},{"issue":"3","key":"bib5","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1016\/j.jtos.2017.05.011","article-title":"TFOS DEWS II pathophysiology report","volume":"15","author":"Bron","year":"2017","journal-title":"Ocul Surf"},{"issue":"4","key":"bib6","doi-asserted-by":"publisher","first-page":"e412","DOI":"10.1111\/aos.13526","article-title":"Dry eye disease and oxidative stress","volume":"96","author":"Seen","year":"2018","journal-title":"Acta Ophthalmol"},{"issue":"5","key":"bib7","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1080\/02713683.2016.1236966","article-title":"Dry eye disease in patients with newly diagnosed depressive disorder","volume":"42","author":"Tiskaoglu","year":"2017","journal-title":"Curr Eye Res"},{"issue":"3","key":"bib8","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1167\/iovs.63.3.3","article-title":"Obstructive sleep apnea affects lacrimal gland function","volume":"63","author":"Wang","year":"2022","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"1","key":"bib9","doi-asserted-by":"publisher","first-page":"3422","DOI":"10.1038\/s41598-019-39467-w","article-title":"Enriched environment alleviates stress-induced dry-eye through the BDNF axis","volume":"9","author":"Sano","year":"2019","journal-title":"Sci Rep"},{"issue":"1","key":"bib10","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.immuni.2018.05.004","article-title":"Sympathetic neuronal activation triggers myeloid progenitor proliferation and differentiation","volume":"49","author":"Vasamsetti","year":"2018","journal-title":"Immunity"},{"issue":"21","key":"bib11","doi-asserted-by":"publisher","first-page":"3597","DOI":"10.1016\/j.neuron.2022.10.017","article-title":"The sympathetic nervous system in the 21st century: neuroimmune interactions in metabolic homeostasis and obesity","volume":"110","author":"Martinez-Sanchez","year":"2022","journal-title":"Neuron"},{"issue":"7876","key":"bib12","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1038\/s41586-021-03830-7","article-title":"Neuro-mesenchymal units control ILC2 and obesity via a brain-adipose circuit","volume":"597","author":"Cardoso","year":"2021","journal-title":"Nature"},{"issue":"3","key":"bib13","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.preteyeres.2009.04.003","article-title":"Neural regulation of lacrimal gland secretory processes: relevance in dry eye diseases","volume":"28","author":"Dartt","year":"2009","journal-title":"Prog Retin Eye Res"},{"issue":"5","key":"bib14","doi-asserted-by":"publisher","first-page":"1050","DOI":"10.1016\/j.immuni.2020.10.013","article-title":"Production of the cytokine VEGF-A by CD4(+) T and myeloid cells disrupts the corneal nerve landscape and promotes herpes stromal keratitis","volume":"53","author":"Yun","year":"2020","journal-title":"Immunity"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"101039","DOI":"10.1016\/j.preteyeres.2021.101039","article-title":"The impact of sensory neuropathy and inflammation on epithelial wound healing in diabetic corneas","volume":"89","author":"Yu","year":"2022","journal-title":"Prog Retin Eye Res"},{"issue":"3","key":"bib16","first-page":"461","article-title":"Sensory and sympathetic innervation of the mammalian cornea. A retrograde tracing study","volume":"30","author":"Marfurt","year":"1989","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"2","key":"bib17","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1167\/iovs.63.2.4","article-title":"Sensory nerve retraction and sympathetic nerve innervation contribute to immunopathology of murine recurrent herpes stromal keratitis","volume":"63","author":"Yun","year":"2022","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"5","key":"bib18","doi-asserted-by":"publisher","first-page":"1496","DOI":"10.1038\/s41385-018-0031-6","article-title":"The mouse autonomic nervous system modulates inflammation and epithelial renewal after corneal abrasion through the activation of distinct local macrophages","volume":"11","author":"Xue","year":"2018","journal-title":"Mucosal Immunol"},{"issue":"13","key":"bib19","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1167\/iovs.62.13.21","article-title":"A hypothalamic-controlled neural reflex promotes corneal inflammation","volume":"62","author":"Lasagni Vitar","year":"2021","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"3","key":"bib20","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1167\/iovs.64.3.20","article-title":"Overactivation of norepinephrine-\u00df2-adrenergic receptor axis promotes corneal neovascularization","volume":"64","author":"Dong","year":"2023","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"3","key":"bib21","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1016\/j.mucimm.2024.02.009","article-title":"Stress systems exacerbate the inflammatory response after corneal abrasion in sleep-deprived mice via the IL-17 signaling pathway","volume":"17","author":"Xue","year":"2024","journal-title":"Mucosal Immunol"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"108048","DOI":"10.1016\/j.exer.2020.108048","article-title":"Corneal epithelial injury-induced norepinephrine promotes Pseudomonas aeruginosa keratitis","volume":"195","author":"Ma","year":"2020","journal-title":"Exp Eye Res"},{"issue":"7965","key":"bib23","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1038\/s41586-023-06110-8","article-title":"Tumour immune rejection triggered by activation of a2-adrenergic receptors","volume":"618","author":"Zhu","year":"2023","journal-title":"Nature"},{"issue":"4","key":"bib24","doi-asserted-by":"publisher","first-page":"1504","DOI":"10.1167\/iovs.05-1634","article-title":"The alpha1- and beta1-adrenergic modulation of lacrimal gland function in the mouse","volume":"48","author":"Ding","year":"2007","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib25","article-title":"Sympathetic signals promote immunosuppressive neutrophils in lung tumors","author":"Liu","year":"2024","journal-title":"bioRxiv Preprint"},{"issue":"12","key":"bib26","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1167\/iovs.64.12.13","article-title":"Sympathetic nerves coordinate corneal epithelial wound healing by controlling the mobilization of ly6chi monocytes from the spleen to the injured cornea","volume":"64","author":"He","year":"2023","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"109391","DOI":"10.1016\/j.exer.2023.109391","article-title":"Involvement of aberrant acinar cell proliferation in scopolamine-induced dry eye mice","volume":"227","author":"Chen","year":"2023","journal-title":"Exp Eye Res"},{"issue":"7","key":"bib28","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1016\/j.ajpath.2023.03.015","article-title":"Hyperglycemia induces tear reduction and dry eye in diabetic mice through the norepinephrine-a(1) adrenergic receptor-mitochondrial impairment axis of lacrimal gland","volume":"193","author":"Zhang","year":"2023","journal-title":"Am J Pathol"},{"key":"bib29","doi-asserted-by":"crossref","DOI":"10.1080\/09273948.2024.2447816","article-title":"Norepinephrine attenuates benzalkonium chloride-induced dry eye disease by regulating the pink1\/parkin mitophagy pathway [published online ahead of print December 27, 2024]","author":"Zhao","year":"2024","journal-title":"Ocul Immunol Inflamm"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"114523","DOI":"10.1016\/j.biopha.2023.114523","article-title":"Interference of sympathetic overactivation restores limbal stem\/progenitor cells function and accelerates corneal epithelial wound healing in diabetic mice","volume":"161","author":"Zhang","year":"2023","journal-title":"Biomed Pharmacother"},{"issue":"5","key":"bib31","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1167\/iovs.64.5.26","article-title":"Norepinephrine as the intrinsic contributor to contact lens-induced pseudomonas aeruginosa keratitis","volume":"64","author":"Zhang","year":"2023","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"108775","DOI":"10.1016\/j.exer.2021.108775","article-title":"Beta-adrenergic glaucoma drugs reduce lymphatic clearance from the eye: a sequential photoacoustic imaging study","volume":"212","author":"Hanna","year":"2021","journal-title":"Exp Eye Res"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1016\/j.freeradbiomed.2021.02.036","article-title":"Hyperglycemia-induced severe mitochondrial bioenergetic deficit of lacrimal gland contributes to the early onset of dry eye in diabetic mice","volume":"166","author":"Qu","year":"2021","journal-title":"Free Radic Biol Med"},{"issue":"12","key":"bib34","doi-asserted-by":"publisher","first-page":"3776","DOI":"10.1167\/iovs.19-26928","article-title":"Therapeutic effects of stat3 inhibition on experimental murine dry eye","volume":"60","author":"Qu","year":"2019","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib35","first-page":"3147","article-title":"Different cellular effects of four anti-inflammatory eye drops on human corneal epithelial cells: independent in active components","volume":"17","author":"Qu","year":"2011","journal-title":"Mol Vis"},{"issue":"9","key":"bib36","doi-asserted-by":"publisher","first-page":"111307","DOI":"10.1016\/j.celrep.2022.111307","article-title":"A synthetic tear protein resolves dry eye through promoting corneal nerve regeneration","volume":"40","author":"Efraim","year":"2022","journal-title":"Cell Rep"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1038\/s42003-018-0270-9","article-title":"Acute tobacco smoke exposure exacerbates the inflammatory response to corneal wounds in mice via the sympathetic nervous system","volume":"2","author":"Xiao","year":"2019","journal-title":"Commun Biol"},{"issue":"2","key":"bib38","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1080\/09273948.2017.1372486","article-title":"Calcitriol, the active metabolite of vitamin D(3), inhibits dry eye related corneal inflammation in vivo and in vitro","volume":"27","author":"Zhang","year":"2019","journal-title":"Ocul Immunol Inflamm"},{"issue":"6","key":"bib39","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1186\/s13075-014-0504-2","article-title":"The sympathetic nervous response in inflammation","volume":"16","author":"Pongratz","year":"2014","journal-title":"Arthritis Res Ther"},{"issue":"7792","key":"bib40","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/s41586-020-1935-3","article-title":"Hyperactivation of sympathetic nerves drives depletion of melanocyte stem cells","volume":"577","author":"Zhang","year":"2020","journal-title":"Nature"},{"issue":"6","key":"bib41","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1007\/s00281-020-00829-6","article-title":"Adrenergic regulation of immune cell function and inflammation","volume":"42","author":"Sharma","year":"2020","journal-title":"Semin Immunopathol"},{"issue":"52","key":"bib42","doi-asserted-by":"publisher","first-page":"15126","DOI":"10.1073\/pnas.1611023114","article-title":"\u00df2-Adrenergic receptor-dependent chemokine receptor 2 expression regulates leukocyte recruitment to the heart following acute injury","volume":"113","author":"Grisanti","year":"2016","journal-title":"Proc Natl Acad Sci USA"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"151087","DOI":"10.1016\/j.bbrc.2024.151087","article-title":"Norepinephrine stimulates M2 macrophage polarization via \u00df2-adrenergic receptor-mediated IL-6 production in breast cancer cells","volume":"741","author":"Park","year":"2024","journal-title":"Biochem Biophys Res Commun"},{"issue":"10","key":"bib44","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1038\/s41419-020-03056-x","article-title":"\u00df(2)-AR blockade potentiates MEK1\/2 inhibitor effect on HNSCC by regulating the Nrf2-mediated defense mechanism","volume":"11","author":"Mele","year":"2020","journal-title":"Cell Death Dis"},{"issue":"1","key":"bib45","doi-asserted-by":"publisher","first-page":"2803","DOI":"10.1038\/s41467-024-47096-9","article-title":"Myeloid-derived suppressor cell mitochondrial fitness governs chemotherapeutic efficacy in hematologic malignancies","volume":"15","author":"Daneshmandi","year":"2024","journal-title":"Nat Commun"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"108294","DOI":"10.1016\/j.exer.2020.108294","article-title":"Inflammatory basis for dry eye disease flares","volume":"201","author":"Perez","year":"2020","journal-title":"Exp Eye Res"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"151609","DOI":"10.1016\/j.aanat.2020.151609","article-title":"Characterization of the innervation of the meibomian glands in humans, rats and mice","volume":"233","author":"Br\u00fcndl","year":"2021","journal-title":"Ann Anat"},{"issue":"5","key":"bib48","doi-asserted-by":"publisher","first-page":"H1031","DOI":"10.1152\/ajpheart.00703.2016","article-title":"Recording sympathetic nerve activity in conscious humans and other mammals: guidelines and the road to standardization","volume":"312","author":"Hart","year":"2017","journal-title":"Am J Physiol Heart Circ Physiol"},{"issue":"7","key":"bib49","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1167\/iovs.64.7.19","article-title":"Autonomic nerve activity features according to dry eye type","volume":"64","author":"Kaido","year":"2023","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"2","key":"bib50","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1167\/iovs.66.2.69","article-title":"Disruption in autonomic nervous activity is associated with central and peripheral-level in dry eye with unstable tear film","volume":"66","author":"Kaido","year":"2025","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.exer.2018.01.008","article-title":"Concentration gradient of noradrenaline from the periphery to the centre of the cornea - a clue to its origin","volume":"168","author":"Figueira","year":"2018","journal-title":"Exp Eye Res"}],"container-title":["Investigative Ophthalmology &amp; Visual Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2803074","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:31:58Z","timestamp":1791927118000},"score":1,"resource":{"primary":{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2803074"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,4]]},"references-count":51,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6,2]]}},"URL":"https:\/\/doi.org\/10.1167\/iovs.66.6.13","relation":{},"ISSN":["1552-5783"],"issn-type":[{"value":"1552-5783","type":"print"}],"subject":[],"published":{"date-parts":[[2025,6,4]]}}}