{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:49:48Z","timestamp":1786668588129,"version":"build-2736575974"},"reference-count":88,"publisher":"Georg Thieme Verlag KG","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Horm Metab Res"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Graves\u2019 orbitopathy (GO), also known as thyroid eye disease is an inflammatory disease of the orbital tissue of the eye that arises as a consequence of autoimmune thyroid disease. The central feature of the disease is the production of antibodies to the thyrotropin hormone receptor (TSHR) that modulate the function of the receptor leading to autoimmune hyperthyroidism and GO. Over the years, all viable preclinical models of Graves\u2019 disease have been incomplete and singularly failed to progress in the treatment of orbital complications. A new mouse model of GO based upon immunogenic presentation of human TSHR A-subunit plasmid by close field electroporation is shown to lead to induction of prolonged functional antibodies to TSHR resulting in chronic disease with subsequent progression to GO. The stable preclinical GO model exhibited pathologies reminiscent of human disease characterized by orbital remodeling by inflammation and adipogenesis. Inflammatory lesions characterized by CD3+ T cells and macrophages were localized in the orbital muscle tissue. This was accompanied by extensive adipogenesis of orbital fat in some immune animals. Surprisingly, other signs of orbital involvement were reminiscent of eyelid inflammation involving chemosis, with dilated and congested orbital blood vessels. More recently, the model is replicated in the author\u2019s independent laboratories. The pre-clinical model will provide the basis to study the pathogenic and regulatory roles of immune T and B cells and their subpopulations to understand the initiation, pathophysiology, and progression of GO.<\/jats:p>","DOI":"10.1055\/s-0035-1555956","type":"journal-article","created":{"date-parts":[[2015,8,19]],"date-time":"2015-08-19T22:59:36Z","timestamp":1440025176000},"page":"797-803","source":"Crossref","is-referenced-by-count":46,"title":["Modeling Graves\u2019 Orbitopathy in Experimental Graves\u2019 Disease"],"prefix":"10.1055","volume":"47","author":[{"given":"S.","family":"Moshkelgosha","sequence":"first","affiliation":[{"name":"Faculty of Life Sciences & Medicine, King\u2019s College London, The Rayne Institute, London, UK"},{"name":"Department of Ophthalmology, University of Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U.","family":"Berchner-Pfannschmidt","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, University of Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Eckstein","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, University of Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. P.","family":"Banga","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences & Medicine, King\u2019s College London, The Rayne Institute, London, UK"},{"name":"Department of Ophthalmology, University of Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2015,8,19]]},"reference":[{"key":"ref1","first-page":"723","article-title":"Diagnosis and management of Graves\u2019 disease: a global overview","volume":"9","author":"L Bartelena","year":"2013","journal-title":"Nature Rev Endocrinol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1056\/NEJM200010263431707","article-title":"Medical progress: Graves\u2019 disease","volume":"343","author":"A P Weetman","year":"2000","journal-title":"New Engl J Med"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1056\/NEJMra0905750","article-title":"Graves\u2019 ophthalmopathy","volume":"362","author":"R S Bahn","year":"2010","journal-title":"New Engl J Med"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1097\/WNO.0000000000000132","article-title":"The pathophysiology of thyroid eye disease","volume":"34","author":"SJ C Shan","year":"2014","journal-title":"J neuroophthalmol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.ophtha.2010.04.004","article-title":"Do subtypes of graves\u2019 orbitopathy exist?","volume":"118","author":"N I Regensburg","year":"2011","journal-title":"Ophthalmol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1089\/thy.2014.0475","article-title":"Role of underlying thyroid disease on the phenotype of Graves\u2019 orbitopathy in a tertiary referral center","volume":"25","author":"M Leo","year":"2015","journal-title":"Thyroid"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1210\/jcem-73-2-307","article-title":"Increased induction of HLA-DR in interferon-gamma in cultured fibroblasts derived from patients with Graves\u2019 ophthalmopathy and pretibial dermopathy","volume":"73","author":"A E Heufelder","year":"1991","journal-title":"J Clin Endocrinol Metab"},{"key":"ref8","first-page":"3428","article-title":"Evidence of adipocyte differentiation in human orbital fibroblasts in primary culture","volume":"81","author":"A Sorisky","year":"1996","journal-title":"J Clin Endocrinol Metab"},{"key":"ref9","first-page":"998","article-title":"Thyrotropin receptor expression in Graves\u2019 orbital adipose\/connective tissues: potential autoantigen in Graves\u2019 ophthalmopathy","volume":"83","author":"R S Bahn","year":"1998","journal-title":"J Clin Endocrinol Metab"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1038\/nrendo.2014.37","article-title":"Thyroid function. 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