{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:01:25Z","timestamp":1791928885395,"version":"4.3.4"},"reference-count":49,"publisher":"Association for Research in Vision and Ophthalmology (ARVO)","issue":"13","license":[{"start":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T00:00:00Z","timestamp":1731974400000},"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":[[2024,11,19]]},"DOI":"10.1167\/iovs.65.13.40","type":"journal-article","created":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T10:49:56Z","timestamp":1732013396000},"page":"40","source":"Crossref","is-referenced-by-count":8,"title":["Tapinarof, an Aryl Hydrocarbon Receptor Ligand, Mitigates Fibroblast Activation in Thyroid Eye Disease: Implications for Novel Therapy"],"prefix":"10.1167","volume":"65","author":[{"given":"Charkira C.","family":"Patrick","sequence":"first","affiliation":[{"name":"Flaum Eye Institute, University of Rochester Medical Center, Rochester, New York, United States"},{"name":"Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Roztocil","sequence":"additional","affiliation":[{"name":"Flaum Eye Institute, University of Rochester Medical Center, Rochester, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farha","family":"Husain","sequence":"additional","affiliation":[{"name":"Flaum Eye Institute, University of Rochester Medical Center, Rochester, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven E.","family":"Feldon","sequence":"additional","affiliation":[{"name":"Flaum Eye Institute, University of Rochester Medical Center, Rochester, New York, United States"},{"name":"Center for Visual Sciences, University of Rochester, Rochester, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Collynn F.","family":"Woeller","sequence":"additional","affiliation":[{"name":"Flaum Eye Institute, University of Rochester Medical Center, Rochester, New York, United States"},{"name":"Center for Visual Sciences, University of Rochester, Rochester, New York, United States"},{"name":"Department of Environmental Medicine, School of Medicine and Dentistry, University of Rochester, Rochester, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"27","reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1089\/thy.2007.0407","article-title":"Immune mechanisms in thyroid eye disease","volume":"18","author":"Lehmann","year":"2008","journal-title":"Thyroid"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1016\/j.survophthal.2021.08.010","article-title":"Thinking inside the box: current insights into targeting orbital tissue remodeling and inflammation in thyroid eye disease","volume":"67","author":"Gupta","year":"2022","journal-title":"Surv Ophthalmol"},{"issue":"4S Suppl 1","key":"bib3","doi-asserted-by":"crossref","first-page":"S13","DOI":"10.1097\/IOP.0000000000001053","article-title":"Thyroid stimulating hormone receptor antibodies in thyroid eye disease \u2014 methodology and clinical applications","volume":"34","author":"Diana","year":"2018","journal-title":"Ophthalmic Plast Reconstr Surg"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1089\/thy.2012.0374","article-title":"Thyrotropin-blocking autoantibodies and thyroid-stimulating autoantibodies: potential mechanisms involved in the pendulum swinging from hypothyroidism to hyperthyroidism or vice versa","volume":"23","author":"McLachlan","year":"2013","journal-title":"Thyroid"},{"key":"bib5","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1055\/s-0035-1555762","article-title":"Current insights into the pathogenesis of Graves' ophthalmopathy","volume":"47","author":"Bahn","year":"2015","journal-title":"Horm Metab Res"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1056\/NEJMra0905750","article-title":"Graves\u2019 ophthalmopathy","volume":"362","author":"Bahn","year":"2010","journal-title":"N Engl J Med"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1159\/000367968","article-title":"Platelet-derived growth factor: a key factor in the pathogenesis of graves' ophthalmopathy and potential target for treatment","volume":"3","author":"Virakul","year":"2014","journal-title":"Eur Thyroid J"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1167\/iovs.62.1.29","article-title":"MicroRNA-130a is elevated in thyroid eye disease and increases lipid accumulation in fibroblasts through the suppression of AMPK","volume":"62","author":"Hammond","year":"2021","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib9","first-page":"222","article-title":"Immunohistochemical analysis of the retrobulbar tissues in Graves' ophthalmopathy","volume":"75","author":"Weetman","year":"1989","journal-title":"Clin Exp Immunol"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1046\/j.1365-2249.1997.4491347.x","article-title":"Analysis of extraocular muscle-infiltrating T cells in thyroid-associated ophthalmopathy (TAO)","volume":"109","author":"Pappa","year":"1997","journal-title":"Clin Exp Immunol"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1056\/NEJMra0905750","article-title":"Graves\u2019 ophthalmopathy","volume":"362","author":"Bahn","year":"2010","journal-title":"N Engl J Med"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"739994","DOI":"10.3389\/fendo.2021.739994","article-title":"Orbital signaling in Graves\u2019 orbitopathy","volume":"12","author":"Draman","year":"2021","journal-title":"Front Endocrinol (Lausanne)"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"167","DOI":"10.3389\/fendo.2016.00167","article-title":"Building the case for insulin-like growth factor receptor-I involvement in thyroid-associated ophthalmopathy","volume":"7","author":"Smith","year":"2017","journal-title":"Front Endocrinol (Lausanne)"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"4336","DOI":"10.1167\/iovs.19-27865","article-title":"TSHR signaling stimulates proliferation through PI3K\/Akt and induction of miR-146a and miR-155 in thyroid eye disease orbital fibroblasts","volume":"60","author":"Woeller","year":"2019","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1097\/WNO.0000000000001134","article-title":"Teprotumumab in clinical practice: recommendations and considerations from the OPTIC trial investigators","volume":"41","author":"Douglas","year":"2021","journal-title":"J Neuroophthalmol"},{"key":"bib16","first-page":"4002","article-title":"Comparison of treatment cost and quality-of-life impact of thyroid eye disease therapies","volume":"63","author":"Shah","year":"2022","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"1748","DOI":"10.1056\/NEJMoa1614949","article-title":"Teprotumumab for thyroid-associated ophthalmopathy","volume":"376","author":"Smith","year":"2017","journal-title":"N Engl J Med"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1056\/NEJMoa1910434","article-title":"Teprotumumab for the treatment of active thyroid eye disease","volume":"382","author":"Douglas","year":"2020","journal-title":"N Engl J Med"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"E400","DOI":"10.1210\/jc.2011-2697","article-title":"Orbit-infiltrating mast cells, monocytes, and macrophages produce PDGF isoforms that orchestrate orbital fibroblast activation in Graves' ophthalmopathy","volume":"97","author":"van Steensel","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"791082","DOI":"10.3389\/ftox.2022.791082","article-title":"More than meets the eye: the aryl hydrocarbon receptor is an environmental sensor, physiological regulator and a therapeutic target in ocular disease","volume":"4","author":"Hammond","year":"2022","journal-title":"Front Toxicol"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"3189","DOI":"10.1016\/j.ajpath.2016.08.017","article-title":"The aryl hydrocarbon receptor and its ligands inhibit myofibroblast formation and activation: implications for thyroid eye disease","volume":"186","author":"Woeller","year":"2016","journal-title":"Am J Pathol"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"e0222779","DOI":"10.1371\/journal.pone.0222779","article-title":"Proton pump inhibitors attenuate myofibroblast formation associated with thyroid eye disease through the aryl hydrocarbon receptor","volume":"14","author":"Hammond","year":"2019","journal-title":"PLoS One"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"2219","DOI":"10.1056\/NEJMoa2103629","article-title":"Phase 3 trials of tapinarof cream for plaque psoriasis","volume":"385","author":"Lebwohl","year":"2021","journal-title":"N Engl J Med"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"2110","DOI":"10.1016\/j.jid.2017.05.004","article-title":"Tapinarof is a natural AhR agonist that resolves skin inflammation in mice and humans","volume":"137","author":"Smith","year":"2017","journal-title":"J Invest Dermatol"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1038\/nprot.2008.73","article-title":"Analyzing real-time PCR data by the comparative C(T) method","volume":"3","author":"Schmittgen","year":"2008","journal-title":"Nat Protoc"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"17623","DOI":"10.1074\/jbc.M702526200","article-title":"Evidence for small ubiquitin-like modifier-dependent nuclear import of the thymidylate biosynthesis pathway","volume":"282","author":"Woeller","year":"2007","journal-title":"J Biol Chem"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"3091","DOI":"10.1167\/iovs.08-2443","article-title":"Imatinib mesylate and AMN107 inhibit PDGF-signaling in orbital fibroblasts: a potential treatment for Graves' ophthalmopathy","volume":"50","author":"van Steensel","year":"2009","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"1942","DOI":"10.1002\/anie.200705148","article-title":"Bacterial biosynthesis of a multipotent stilbene","volume":"47","author":"Joyce","year":"2008","journal-title":"Angew Chem Int Ed Engl"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"8432","DOI":"10.1074\/jbc.275.12.8432","article-title":"2,3,7,8-tetrachlorodibenzo-p-dioxin-induced degradation of aryl hydrocarbon receptor (AhR) by the ubiquitin-proteasome pathway. Role of the transcription activation and DNA binding of AhR","volume":"275","author":"Ma","year":"2000","journal-title":"J Biol Chem"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"8477","DOI":"10.1038\/s41598-020-65414-1","article-title":"The aryl hydrocarbon receptor pathway controls matrix metalloproteinase-1 and collagen levels in human orbital fibroblasts","volume":"10","author":"Roztocil","year":"2020","journal-title":"Sci Rep"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"6549","DOI":"10.1167\/iovs.15-16610","article-title":"Orbital fibroblasts from graves' orbitopathy patients share functional and immunophenotypic properties with mesenchymal stem\/stromal cells","volume":"56","author":"Brandau","year":"2015","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1089\/thy.2007.0404","article-title":"Unique attributes of orbital fibroblasts and global alterations in IGF-1 receptor signaling could explain thyroid-associated ophthalmopathy","volume":"18","author":"Smith","year":"2008","journal-title":"Thyroid"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1167\/iovs.15-18157","article-title":"PDGF-BB enhances the proliferation of cells in human orbital fibroblasts by suppressing PDCD4 expression via up-regulation of microRNA-21","volume":"57","author":"Lee","year":"2016","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"E944","DOI":"10.1210\/jc.2012-1020","article-title":"PDGF enhances orbital fibroblast responses to TSHR stimulating autoantibodies in Graves\u2019 ophthalmopathy patients","volume":"97","author":"van Steensel","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"202","DOI":"10.3109\/01676831003668443","article-title":"The orbital fibroblast: a key player and target for therapy in Graves\u2019","volume":"29","author":"van Steensel","year":"2010","journal-title":"Orbit"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"2254","DOI":"10.2353\/ajpath.2006.060196","article-title":"Platelet-derived growth factor-beta receptor activation is essential for fibroblast and pericyte recruitment during cutaneous wound healing","volume":"169","author":"Rajkumar","year":"2006","journal-title":"Am J Pathol"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-3-319-91439-8","article-title":"Imatinib mesylate","volume":"212","author":"Waller","year":"2018","journal-title":"Recent Results Cancer Res"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-3-642-54490-3","article-title":"Imatinib mesylate","volume":"201","author":"Waller","year":"2014","journal-title":"Recent Results Cancer Res"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"1680","DOI":"10.1002\/ajh.27378","article-title":"Toxicities associated with tyrosine kinase inhibitor maintenance following allogeneic hematopoietic cell transplantation in Philadelphia chromosome-positive acute lymphoblastic leukemia","volume":"99","author":"Othman","year":"2024","journal-title":"Am J Hematol"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.bcp.2019.06.015","article-title":"Aryl hydrocarbon receptor (AHR): from selected human target genes and crosstalk with transcription factors to multiple AHR functions","volume":"168","author":"Bock","year":"2019","journal-title":"Biochem Pharmacol"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"3087","DOI":"10.1096\/fj.08-109009","article-title":"Crosstalk between AHR and Wnt signaling through R-Spondin1 impairs tissue regeneration in zebrafish","volume":"22","author":"Mathew","year":"2008","journal-title":"FASEB J"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jaci.2023.12.013","article-title":"Tapinarof validates the aryl hydrocarbon receptor as a therapeutic target: a clinical review","volume":"154","author":"Silverberg","year":"2024","journal-title":"J Allergy Clin Immunol"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.2353\/ajpath.2006.060434","article-title":"Activated human T lymphocytes express cyclooxygenase-2 and produce proadipogenic prostaglandins that drive human orbital fibroblast differentiation to adipocytes","volume":"169","author":"Feldon","year":"2006","journal-title":"Am J Pathol"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"9622","DOI":"10.1038\/s41598-019-46075-1","article-title":"Macrophages promote a profibrotic phenotype in orbital fibroblasts through increased hyaluronic acid production and cell contractility","volume":"9","author":"Yang","year":"2019","journal-title":"Sci Rep"},{"key":"bib45","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1055\/s-0035-1555956","article-title":"Modeling Graves\u2019 orbitopathy in experimental Graves\u2019 disease","volume":"47","author":"Banga","year":"2015","journal-title":"Horm Metab Res"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"13096","DOI":"10.1038\/s41598-018-31253-4","article-title":"Graves\u2019 orbitopathy occurs sex-independently in an autoimmune hyperthyroid mouse model","volume":"8","author":"Schluter","year":"2018","journal-title":"Sci Rep"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"1211473","DOI":"10.3389\/fendo.2023.1211473","article-title":"Linsitinib, an IGF-1R inhibitor, attenuates disease development and progression in a model of thyroid eye disease","volume":"14","author":"Gulbins","year":"2023","journal-title":"Front Endocrinol (Lausanne)"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.imlet.2023.09.005","article-title":"Single-cell communication patterns and their intracellular information flow in synovial fibroblastic osteoarthritis and rheumatoid arthritis","volume":"263","author":"Wang","year":"2023","journal-title":"Immunol Lett"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.3390\/biom10081093","article-title":"Lysyl oxidase (LOX): functional contributions to signaling pathways","volume":"10","author":"Laczko","year":"2020","journal-title":"Biomolecules"}],"container-title":["Investigative Ophthalmology &amp; Visual Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2802260","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:31:54Z","timestamp":1791927114000},"score":1,"resource":{"primary":{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2802260"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,19]]},"references-count":49,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2024,11,4]]}},"URL":"https:\/\/doi.org\/10.1167\/iovs.65.13.40","relation":{},"ISSN":["1552-5783"],"issn-type":[{"value":"1552-5783","type":"print"}],"subject":[],"published":{"date-parts":[[2024,11,19]]}}}