{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:02:19Z","timestamp":1791928939880,"version":"4.3.4"},"reference-count":55,"publisher":"Association for Research in Vision and Ophthalmology (ARVO)","issue":"11","license":[{"start":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:00:00Z","timestamp":1756080000000},"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":[[2025,8,25]]},"DOI":"10.1167\/iovs.66.11.57","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T14:30:38Z","timestamp":1756132238000},"page":"57","source":"Crossref","is-referenced-by-count":3,"title":["Targeted Delivery of CD34 Aptamer-Coupled Tocilizumab Microspheres for Effective Treatment of Thyroid-Associated Ophthalmopathy"],"prefix":"10.1167","volume":"66","author":[{"given":"Yong","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Third Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayang","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Third Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiamin","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Third Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingyu","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Third Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Third Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sha","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Third Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Third Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Third Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Third Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"27","reference":[{"issue":"3","key":"bib1","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1001\/archopht.120.3.380","article-title":"Insights into the pathogenesis of thyroid-associated orbitopathy: evolving rationale for therapy","volume":"120","author":"Kazim","year":"2002","journal-title":"Arch Ophthalmol"},{"issue":"16","key":"bib2","doi-asserted-by":"publisher","first-page":"1552","DOI":"10.1056\/NEJMra1510030","article-title":"Graves\u2019 disease","volume":"375","author":"Smith","year":"2016","journal-title":"N Engl J Med"},{"issue":"8867","key":"bib3","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/0140-6736(93)91475-2","article-title":"Expression of thyrotropin-receptor mRNA in healthy and Graves\u2019 disease retro-orbital tissue","volume":"342","author":"Feliciello","year":"1993","journal-title":"Lancet"},{"issue":"4","key":"bib4","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1089\/thy.1993.3.297","article-title":"Detection of TSH receptor RNA in cultured fibroblasts from patients with Graves\u2019 ophthalmopathy and pretibial dermopathy","volume":"3","author":"Heufelder","year":"1993","journal-title":"Thyroid"},{"issue":"1","key":"bib5","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1089\/thy.2009.0278","article-title":"A stimulatory thyrotropin receptor antibody (M22) and thyrotropin increase interleukin-6 expression and secretion in Graves\u2019 orbital preadipocyte fibroblasts","volume":"20","author":"Kumar","year":"2010","journal-title":"Thyroid"},{"issue":"10","key":"bib6","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1089\/105072501753210984","article-title":"Interleukin-6 stimulates thyrotropin receptor expression in human orbital preadipocyte fibroblasts from patients with Graves\u2019 ophthalmopathy","volume":"11","author":"Jyonouchi","year":"2001","journal-title":"Thyroid"},{"issue":"2","key":"bib7","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1097\/IOP.0000000000000037","article-title":"Treatment of active corticosteroid-resistant graves\u2019 orbitopathy","volume":"30","author":"Perez-Moreiras","year":"2014","journal-title":"Ophthalmic Plast Reconstr Surg"},{"issue":"1","key":"bib8","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1186\/s13287-018-0835-z","article-title":"The emerging role of fibrocytes in ocular disorders","volume":"9","author":"Zhang","year":"2018","journal-title":"Stem Cell Res Ther"},{"issue":"11","key":"bib9","doi-asserted-by":"publisher","first-page":"4999","DOI":"10.1167\/iovs.16-19798","article-title":"Fibrocytes and fibrovascular membrane formation in proliferative diabetic retinopathy","volume":"57","author":"Tamaki","year":"2016","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"1","key":"bib10","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1210\/jc.2009-1614","article-title":"Increased generation of fibrocytes in thyroid-associated ophthalmopathy","volume":"95","author":"Douglas","year":"2010","journal-title":"J Clin Endocrinol Metab"},{"issue":"19","key":"bib11","doi-asserted-by":"publisher","first-page":"7427","DOI":"10.1073\/pnas.1202064109","article-title":"Human fibrocytes coexpress thyroglobulin and thyrotropin receptor","volume":"109","author":"Fernando","year":"2012","journal-title":"Proc Natl Acad Sci USA"},{"issue":"6","key":"bib12","doi-asserted-by":"publisher","first-page":"2615","DOI":"10.1167\/iovs.18-23951","article-title":"CD34- orbital fibroblasts from patients with thyroid-associated ophthalmopathy modulate TNF-alpha expression in CD34+ fibroblasts and fibrocytes","volume":"59","author":"Lu","year":"2018","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"1","key":"bib13","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1089\/107632701300003269","article-title":"Biodegradable polymer scaffolds with well-defined interconnected spherical pore network","volume":"7","author":"Ma","year":"2001","journal-title":"Tissue Eng"},{"issue":"12","key":"bib14","doi-asserted-by":"publisher","first-page":"2728","DOI":"10.3390\/pharmaceutics14122728","article-title":"PLGA-based nanomedicine: history of advancement and development in clinical applications of multiple diseases","volume":"14","author":"Alsaab","year":"2022","journal-title":"Pharmaceutics"},{"issue":"3","key":"bib15","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1038\/nrd.2016.199","article-title":"Aptamers as targeted therapeutics: current potential and challenges","volume":"16","author":"Zhou","year":"2017","journal-title":"Nat Rev Drug Discov"},{"issue":"3","key":"bib16","first-page":"193","article-title":"Recent progress and opportunities for nucleic acid aptamers","volume":"11","author":"Byun","year":"2021","journal-title":"Life (Basel)"},{"issue":"12","key":"bib17","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1038\/labinvest.2009.113","article-title":"Using an RNA aptamer probe for flow cytometry detection of CD30-expressing lymphoma cells","volume":"89","author":"Zhang","year":"2009","journal-title":"Lab Invest"},{"issue":"2","key":"bib18","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1006\/abio.2001.5169","article-title":"Aptamer beacons for the direct detection of proteins","volume":"294","author":"Hamaguchi","year":"2001","journal-title":"Anal Biochem"},{"issue":"10","key":"bib19","doi-asserted-by":"publisher","first-page":"3138","DOI":"10.1021\/ja056957p","article-title":"An electronic, aptamer-based small-molecule sensor for the rapid, label-free detection of cocaine in adulterated samples and biological fluids","volume":"128","author":"Baker","year":"2006","journal-title":"J Am Chem Soc"},{"issue":"3","key":"bib20","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1530\/JOE-11-0162","article-title":"Orbital fibrosis in a mouse model of Graves\u2019 disease induced by genetic immunization of thyrotropin receptor cDNA","volume":"210","author":"Zhao","year":"2011","journal-title":"J Endocrinol"},{"issue":"8","key":"bib21","doi-asserted-by":"publisher","first-page":"1428","DOI":"10.1038\/nprot.2016.081","article-title":"High-mass-resolution MALDI mass spectrometry imaging of metabolites from formalin-fixed paraffin-embedded tissue","volume":"11","author":"Ly","year":"2016","journal-title":"Nat Protoc"},{"issue":"2","key":"bib22","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1167\/iovs.65.2.25","article-title":"SOX9 induces orbital fibroblast activation in thyroid eye disease via MAPK\/ERK1\/2 pathway","volume":"65","author":"Zhou","year":"2024","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"111780","DOI":"10.1016\/j.mce.2022.111780","article-title":"The miR-103a-3p\/TGFBR3 axis regulates TGF-\u00df-induced orbital fibroblast activation and fibrosis in thyroid-eye disease","volume":"559","author":"Xie","year":"2023","journal-title":"Mol Cell Endocrinol"},{"issue":"6","key":"bib24","doi-asserted-by":"publisher","first-page":"2615","DOI":"10.1167\/iovs.18-23951","article-title":"CD34- orbital fibroblasts from patients with thyroid-associated ophthalmopathy modulate TNF-a expression in CD34+ fibroblasts and fibrocytes","volume":"59","author":"Lu","year":"2018","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"3577","DOI":"10.2147\/IJN.S446656","article-title":"A TSHR-targeting aptamer in monocytes correlating with clinical activity in TAO","volume":"19","author":"Cao","year":"2024","journal-title":"Int J Nanomedicine"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"123302","DOI":"10.1016\/j.talanta.2022.123302","article-title":"Rapid screening of aptamers for fluorescent targets by integrated digital PCR and flow cytometry","volume":"242","author":"Fang","year":"2022","journal-title":"Talanta"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"581","DOI":"10.2147\/IJN.S495204","article-title":"Gelatin\/poly (lactic-co-glycolic acid)\/attapulgite composite scaffold equipped with teriparatide microspheres for osteogenesis in vitro and in vivo","volume":"20","author":"Zhao","year":"2025","journal-title":"Int J Nanomedicine"},{"issue":"6","key":"bib28","doi-asserted-by":"publisher","first-page":"3643","DOI":"10.1021\/acsbiomaterials.3c00030","article-title":"sprayable berberine-silk fibroin microspheres with extracellular matrix anchoring function accelerate infected wound healing through antibacterial and anti-inflammatory effects","volume":"9","author":"Sang","year":"2023","journal-title":"ACS Biomater Sci Eng"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"125244","DOI":"10.1016\/j.talanta.2023.125244","article-title":"Aptamer-thrombin loaded magnetic microspheres for bio-specific extraction and precise detection of hirudin","volume":"267","author":"Cao","year":"2024","journal-title":"Talanta"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"891922","DOI":"10.3389\/fendo.2022.891922","article-title":"Dihydroartemisinin exerts antifibrotic and anti-inflammatory effects in Graves\u2019 ophthalmopathy by targeting orbital fibroblasts","volume":"13","author":"Yang","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"e18535","DOI":"10.7717\/peerj.18535","article-title":"miR-101-3p suppresses proliferation of orbital fibroblasts by targeting pentraxin-3 in thyroid eye disease","volume":"12","author":"Zhu","year":"2024","journal-title":"PeerJ"},{"issue":"1","key":"bib32","doi-asserted-by":"publisher","first-page":"245","DOI":"10.21037\/gs-21-908","article-title":"Lysyl oxidase promotes anaplastic thyroid carcinoma cell proliferation and metastasis mediated via BMP1","volume":"11","author":"Liu","year":"2022","journal-title":"Gland Surg"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"e2711","DOI":"10.1210\/clinem\/dgae732","article-title":"2'-O-Galloylhyperin prevents tissue remodeling in thyroid eye disease: prospects as a thyrotropin receptor antagonist","volume":"110","author":"Guo","year":"2025","journal-title":"J Clin Endocrinol Metab"},{"issue":"2","key":"bib34","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.jdermsci.2022.04.004","article-title":"HOXA11-AS facilitates the proliferation, cell cycle process and migration of keloid fibroblasts through sponging miR-188-5p to regulate VEGFA","volume":"106","author":"Zhou","year":"2022","journal-title":"J Dermatol Sci"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.placenta.2023.11.010","article-title":"USP17 regulates preeclampsia by modulating the NF-?B signaling pathway via deubiquitinating HDAC2","volume":"145","author":"Li","year":"2024","journal-title":"Placenta"},{"issue":"12","key":"bib36","doi-asserted-by":"publisher","first-page":"1897","DOI":"10.1172\/JCI200317069","article-title":"The thyrotropin receptor autoantigen in Graves disease is the culprit as well as the victim","volume":"111","author":"Chen","year":"2003","journal-title":"J Clin Invest"},{"issue":"2","key":"bib37","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1007\/s40618-022-01902-7","article-title":"The role and molecular mechanism of gut microbiota in Graves\u2019 orbitopathy","volume":"46","author":"Li","year":"2023","journal-title":"J Endocrinol Invest"},{"issue":"3","key":"bib38","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1089\/thy.2015.0620","article-title":"The influence of dihydrotestosterone on the development of Graves\u2019 disease in female BALB\/c mice","volume":"26","author":"Liu","year":"2016","journal-title":"Thyroid"},{"issue":"9","key":"bib39","doi-asserted-by":"publisher","first-page":"e75100","DOI":"10.1371\/journal.pone.0075100","article-title":"Thyrotropin regulates IL-6 expression in CD34+ fibrocytes: clear delineation of its cAMP-independent actions","volume":"8","author":"Raychaudhuri","year":"2013","journal-title":"PLoS One"},{"issue":"1","key":"bib40","doi-asserted-by":"publisher","first-page":"37","DOI":"10.5603\/FHC.a2020.0003","article-title":"Search of reference biomarkers reflecting orbital tissue remodeling in the course of Graves\u2019 orbitopathy","volume":"58","author":"Pawlowski","year":"2020","journal-title":"Folia Histochem Cytobiol"},{"issue":"16","key":"bib41","doi-asserted-by":"publisher","first-page":"8362","DOI":"10.1093\/nar\/gkz688","article-title":"Molecular affinity rulers: systematic evaluation of DNA aptamers for their applicabilities in ELISA","volume":"47","author":"Kimoto","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"113742","DOI":"10.1016\/j.ab.2020.113742","article-title":"Mathematical approaches in estimating aptamer-target binding affinity","volume":"600","author":"Thevendran","year":"2020","journal-title":"Anal Biochem"},{"issue":"5","key":"bib43","doi-asserted-by":"publisher","first-page":"e0232612","DOI":"10.1371\/journal.pone.0232612","article-title":"Tocilizumab does not block interleukin-6 (IL-6) signaling in murine cells","volume":"15","author":"Lokau","year":"2020","journal-title":"PLoS One"},{"issue":"5454","key":"bib44","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1126\/science.287.5454.820","article-title":"Adaptive recognition by nucleic acid aptamers","volume":"287","author":"Hermann","year":"2000","journal-title":"Science"},{"issue":"7552","key":"bib45","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1038\/521274a","article-title":"Reproducibility crisis: blame it on the antibodies","volume":"521","author":"Baker","year":"2015","journal-title":"Nature"},{"issue":"6","key":"bib46","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1038\/nrneph.2009.74","article-title":"Fibroblast activation and myofibroblast generation in obstructive nephropathy","volume":"5","author":"Grande","year":"2009","journal-title":"Nat Rev Nephrol"},{"issue":"3","key":"bib47","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1007\/s00441-016-2467-x","article-title":"Fibroblast activation in cancer: when seed fertilizes soil","volume":"365","author":"Kuzet","year":"2016","journal-title":"Cell Tissue Res"},{"issue":"6","key":"bib48","doi-asserted-by":"publisher","first-page":"3288","DOI":"10.3390\/ijms25063288","article-title":"The role of fibrogenesis and extracellular matrix proteins in the pathogenesis of Graves\u2019 ophthalmopathy","volume":"25","author":"Chiu","year":"2024","journal-title":"Int J Mol Sci"},{"issue":"2","key":"bib49","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1159\/000522417","article-title":"Metabolic regulation of fibroblast activation and proliferation during organ fibrosis","volume":"8","author":"Wang","year":"2022","journal-title":"Kidney Dis (Basel)"},{"issue":"6","key":"bib50","doi-asserted-by":"publisher","first-page":"3061","DOI":"10.1167\/iovs.09-4257","article-title":"Antifibrotic effect of pirfenidone on orbital fibroblasts of patients with thyroid-associated ophthalmopathy by decreasing TIMP-1 and collagen levels","volume":"51","author":"Kim","year":"2010","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"8","key":"bib51","doi-asserted-by":"publisher","first-page":"2299","DOI":"10.3390\/ijms19082299","article-title":"Contribution of STAT3 to inflammatory and fibrotic diseases and prospects for its targeting for treatment","volume":"19","author":"Kasembeli","year":"2018","journal-title":"Int J Mol Sci"},{"key":"bib52","doi-asserted-by":"publisher","first-page":"111363","DOI":"10.1016\/j.mce.2021.111363","article-title":"Signal transducer and activator of transcription 3 as a potential therapeutic target for Graves\u2019 orbitopathy","volume":"534","author":"Ko","year":"2021","journal-title":"Mol Cell Endocrinol"},{"issue":"1","key":"bib53","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.immuni.2013.10.022","article-title":"Interleukin-6 signaling drives fibrosis in unresolved inflammation","volume":"40","author":"Fielding","year":"2014","journal-title":"Immunity"},{"key":"bib54","doi-asserted-by":"publisher","first-page":"1452849","DOI":"10.3389\/fimmu.2024.1452849","article-title":"IL6 receptor inhibitors: exploring the therapeutic potential across multiple diseases through drug target Mendelian randomization","volume":"15","author":"Fu","year":"2024","journal-title":"Front Immunol"},{"issue":"1","key":"bib55","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1186\/s12967-023-04217-0","article-title":"RNA aptamers with specific binding affinity to CD40 (CD40Apt) represents a promising antagonist of the CD40-CD40L signaling for thyroid-associated ophthalmopathy (TAO) treatment in mouse","volume":"21","author":"Chen","year":"2023","journal-title":"J Transl Med"}],"container-title":["Investigative Ophthalmology &amp; Visual Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2810716","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:32:08Z","timestamp":1791927128000},"score":1,"resource":{"primary":{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2810716"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,25]]},"references-count":55,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,8,1]]}},"URL":"https:\/\/doi.org\/10.1167\/iovs.66.11.57","relation":{},"ISSN":["1552-5783"],"issn-type":[{"value":"1552-5783","type":"print"}],"subject":[],"published":{"date-parts":[[2025,8,25]]}}}