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重视甲状腺相关眼病的基础研究和药物研发
范先群
作者及单位信息
·
DOI： 10.3760/cma.j.cn115989-20200812-00582
The importance of basic research and drug development for thyroid-associated ophthalmopathy
Fan Xianqun
Authors Info & Affiliations
Fan Xianqun
Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai 200011, China
·
DOI： 10.3760/cma.j.cn115989-20200812-00582
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摘要

甲状腺相关眼病(TAO)是一种器官特异性自身免疫性疾病，发病机制复杂，近年来关于TAO发病机制研究已取得长足的进步，对其发病和进展的免疫机制和分子基础有了深入的了解和认识，包括相关的自身抗原、淋巴细胞、炎性因子和自身免疫的靶组织，即眼眶成纤维细胞(OF)的作用和生物学行为的新概念等。基于TAO的发病机制研究，近年来靶向TAO发病机制不同环节的诊疗研究为TAO的治疗带来了新的希望，一些新的靶向生物制剂和免疫抑制剂也逐渐进入临床试验并呈现出良好的效果和较少的不良反应。虽然TAO的相关研究成果令人兴奋，但是多数新药仍未达到广泛用于临床的阶段，TAO的无创治疗仍是我们面临的巨大挑战。我们应在前期研究的基础上进一步加强TAO基础研究，完善TAO的动物模型建立方法，全面认识其发病机制，进一步研发更具针对性的治疗药物，开展TAO的精准临床诊疗研究，改善患者预后。

甲状腺相关眼病;Graves眼病;发病机制;药物研发
ABSTRACT

Thyroid-associated ophthalmopathy (TAO) is an organ specific autoimmune disease with complex pathogenesis.In recent years, great progress has been made in the pathogenesis of TAO primarily in immune and molecular mechanism aspects, including related autoantigens, lymphocytes, inflammatory factors, and autoimmune target tissue, that is, the role and biological behavior of orbital fibroblasts.Accordingly, various biological agents and immunosuppressive agents have emerged in an endless stream and have shown good effects and safety in clinical trials.Some important researches seem to be promising, but many novel therapies still are not extensively applied in clinical practice up to now.Therefore, it is of great significance to strengthen the basic research of TAO, fully understand its pathogenesis, research and develop more targeting drugs and precise clinical diagnosis and management of TAO, as well as improve the prognosis of patients.

Thyroid-associated ophthalmopathy;Graves disease;Pathogenesis;Research and development of drugs
Fan Xianqun, Email: mocdef.6ab21nuqnaixnafrd
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引用本文

范先群. 重视甲状腺相关眼病的基础研究和药物研发[J]. 中华实验眼科杂志,2020,38(11)：905-909.

DOI:10.3760/cma.j.cn115989-20200812-00582

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甲状腺相关眼病(thyroid-associated ophthalmopathy，TAO)是弥漫性毒性甲状腺肿，即Graves病(Graves disease，GD)常见的甲状腺外临床表现，其发生率占GD患者的25%～50%，又称Graves眼病(Graves ophthalmopathy，GO)。除此之外，TAO还可见于2%的慢性甲状腺炎患者和少数甲状腺功能正常者 [ 1 ]。TAO是一种组织特异性自身免疫性疾病，具体发病机制尚未完全阐明，目前认为其与遗传、免疫和环境等多种因素有关 [ 1 ]。TAO临床表现复杂，包括眼睑退缩、眼球突出、复视、限制性斜视、暴露性角膜炎和压迫性视神经病变等 [ 2 ]。欧洲Graves眼病协作组(The European Group on Graves' Orbitopathy，EUGOGO)依据病情对患者生活质量的影响及该病导致视力丧失的风险将TAO分为轻度、中重度和极重度 [ 3 ]。重视TAO的发病机制研究对疾病的诊疗进步具有重要意义。近年来，关于TAO发病机制研究更加深入，提出了一些新的概念和认识，TAO发病和进展过程中体内细胞亚群分布及其分子机制研究受到了更多关注，如纤维细胞、辅助性T细胞(T helper cell，Th)17和胰岛素样生长因子1受体(insulin-like growth factor-1 receptor，IGF-1R)等在TAO发病和进展中的作用正逐步被国内外研究者证实，围绕相关靶点研发新型TAO治疗药物也成为研究的热点。
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参考文献
[1]
Hiromatsu Y , Eguchi H , Tani J ，et al. Graves' ophthalmopathy：epidemiology and natural history[J]．Intern Med， 2014，53(5):353-360. DOI： 10.2169/internalmedicine.53.1518 .
返回引文位置Google Scholar
百度学术
万方数据
[2]
Wang Y , Smith TJ . Current concepts in the molecular pathogenesis of thyroid-associated ophthalmopathy[J]．Invest Ophthalmol Vis Sci， 2014，55(3):1735-1748. DOI： 10.1167/iovs.14-14002 .
返回引文位置Google Scholar
百度学术
万方数据
[3]
Bartalena L , Baldeschi L , Boboridis K ，et al. The 2016 European Thyroid Association/European Group on Graves' Orbitopathy Guidelines for the Management of Graves' Orbitopathy[J]．Eur Thyroid J， 2016，5(1):9-26. DOI： 10.1159/000443828 .
返回引文位置Google Scholar
百度学术
万方数据
[4]
Wiersinga WM . Autoimmunity in Graves' ophthalmopathy：the result of an unfortunate marriage between TSH receptors and IGF-1 receptors？[J]．J Clin Endocrinol Metab， 2011，96(8):2386-2394. DOI： 10.1210/jc.2011-0307 .
返回引文位置Google Scholar
百度学术
万方数据
[5]
Pritchard J , Han R , Horst N ，et al. Immunoglobulin activation of T cell chemoattractant expression in fibroblasts from patients with Graves' disease is mediated through the insulin-like growth factor I receptor pathway[J]．J Immunol， 2003，170(12):6348-6354. DOI： 10.4049/jimmunol.170.12.6348 .
返回引文位置Google Scholar
百度学术
万方数据
[6]
Lehmann GM , Feldon SE , Smith TJ ，et al. Immune mechanisms in thyroid eye disease[J]．Thyroid， 2008，18(9):959-965. DOI： 10.1089/thy.2007.0407 .
返回引文位置Google Scholar
百度学术
万方数据
[7]
Huber AK , Jacobson EM , Jazdzewski K ，et al. Interleukin (IL)-23 receptor is a major susceptibility gene for Graves' ophthalmopathy：the IL-23/T-helper 17 axis extends to thyroid autoimmunity[J]．J Clin Endocrinol Metab， 2008，93(3):1077-1081. DOI： 10.1210/jc.2007-2190 .
返回引文位置Google Scholar
百度学术
万方数据
[8]
Shen J , Li Z , Li W ，et al. Th1，Th2，and Th17 cytokine involvement in thyroid associated ophthalmopathy[J/OL]．Dis Markers， 2015，2015:609593[2020-07-21]. https://pubmed.ncbi.nlm.nih.gov/26089587/. DOI： 10.1155/2015/609593 .
返回引文位置Google Scholar
百度学术
万方数据
[9]
Wei H , Guan M , Qin Y ，et al. Circulating levels of miR-146a and IL-17 are significantly correlated with the clinical activity of Graves' ophthalmopathy[J]．Endocr J， 2014，61(11):1087-1092. DOI： 10.1507/endocrj.ej14-0246 .
返回引文位置Google Scholar
百度学术
万方数据
[10]
Huang D , Luo Q , Yang H ，et al. Changes of lacrimal gland and tear inflammatory cytokines in thyroid-associated ophthalmopathy[J]．Invest Ophthalmol Vis Sci， 2014，55(8):4935-4943. DOI： 10.1167/iovs.13-13704 .
返回引文位置Google Scholar
百度学术
万方数据
[11]
Fang S , Huang Y , Wang S ，et al. IL-17A exacerbates fibrosis by promoting the proinflammatory and profibrotic function of orbital fibroblasts in TAO[J]．J Clin Endocrinol Metab， 2016，101(8):2955-2965. DOI： 10.1210/jc.2016-1882 .
返回引文位置Google Scholar
百度学术
万方数据
[12]
Fang S , Huang Y , Zhong S ，et al. IL-17A promotes RANTES expression，but not IL-16，in orbital fibroblasts via CD40-CD40L combination in thyroid-associated ophthalmopathy[J]．Invest Ophthalmol Vis Sci， 2016，57(14):6123-6133. DOI： 10.1167/iovs.16-20199 .
返回引文位置Google Scholar
百度学术
万方数据
[13]
Fang S , Huang Y , Zhong S ，et al. Regulation of orbital fibrosis and adipogenesis by pathogenic Th17 cells in graves orbitopathy[J]．J Clin Endocrinol Metab， 2017，102(11):4273-4283. DOI： 10.1210/jc.2017-01349 .
返回引文位置Google Scholar
百度学术
万方数据
[14]
Xin Z , Hua L , Shi TT ，et al. A genome-wide DNA methylation analysis in peripheral blood from patients identifies risk loci associated with Graves' orbitopathy[J]．J Endocrinol Invest， 2018，41(6):719-727. DOI： 10.1007/s40618-017-0796-6 .
返回引文位置Google Scholar
百度学术
万方数据
[15]
Luo LH , Li DM , Wang YL ，et al. Tim3/galectin-9 alleviates the inflammation of TAO patients via suppressing Akt/NF-kB signaling pathwa y [J]．Biochem Biophys Res Commun， 2017，491(4):966-972. DOI： 10.1016/j.bbrc.2017.07.144 .
返回引文位置Google Scholar
百度学术
万方数据
[16]
Zhao J , Lin B , Deng H ，et al. Decreased expression of TIM-3 on Th17 cells associated with ophthalmopathy in patients with Graves' disease[J]．Curr Mol Med， 2018，18(2):83-90. DOI： 10.2174/1566524018666180705105753 .
返回引文位置Google Scholar
百度学术
万方数据
[17]
Dik WA , Virakul S , van Steensel L ．Current perspectives on the role of orbital fibroblasts in the pathogenesis of Graves' ophthalmopathy[J]．Exp Eye Res， 2016，142:83-91. DOI： 10.1016/j.exer.2015.02.007 .
返回引文位置Google Scholar
百度学术
万方数据
[18]
Fang S , Huang Y , Wang N ，et al. Insights into local orbital immunity：evidence for the involvement of the Th17 cell pathway in thyroid-associated ophthalmopathy[J]．J Clin Endocrinol Metab， 2019，104(5):1697-1711. DOI： 10.1210/jc.2018-01626 .
返回引文位置Google Scholar
百度学术
万方数据
[19]
Wang HS , Cao HJ , Winn VD ，et al. Leukoregulin induction of prostaglandin-endoperoxide H synthase-2 in human orbital fibroblasts.An in vitro model for connective tissue inflammation [J]．J Biol Chem， 1996，271(37):22718-22728.
返回引文位置Google Scholar
百度学术
万方数据
[20]
Raychaudhuri N , Douglas RS , Smith TJ . PGE2 induces IL-6 in orbital fibroblasts through EP2 receptors and increased gene promoter activity：implications to thyroid-associated ophthalmopathy[J/OL]．PLoS One， 2010，5(12):e15296[2020-07-19]. https://pubmed.ncbi.nlm.nih.gov/21209948/. DOI： 10.1371/journal.pone.0015296 .
返回引文位置Google Scholar
百度学术
万方数据
[21]
Khoo TK , Coenen MJ , Schiefer AR ，et al. Evidence for enhanced Thy-1 (CD90) expression in orbital fibroblasts of patients with Graves' ophthalmopathy[J]．Thyroid， 2008，18(12):1291-1296. DOI： 10.1089/thy.2008.0255 .
返回引文位置Google Scholar
百度学术
万方数据
[22]
Antonelli A , Rotondi M , Ferrari SM ，et al. Interferon-gamma-inducible alpha-chemokine CXCL10 involvement in Graves' ophthalmopathy：modulation by peroxisome proliferator-activated receptor-gamma agonists[J]．J Clin Endocrinol Metab， 2006，91(2):614-620. DOI： 10.1210/jc.2005-1689 .
返回引文位置Google Scholar
百度学术
万方数据
[23]
Antonelli A , Ferrari SM , Fallahi P ，et al. Monokine induced by interferon gamma (IFNgamma) (CXCL9) and IFNgamma inducible T-cell alpha-chemoattractant (CXCL11) involvement in Graves' disease and ophthalmopathy：modulation by peroxisome proliferator-activated receptor-gamma agonists[J]．J Clin Endocrinol Metab， 2009，94(5):1803-1809. DOI： 10.1210/jc.2008-2450 .
返回引文位置Google Scholar
百度学术
万方数据
[24]
Smith TJ , Hegedüs L ．Graves' disease[J]．N Engl J Med， 2016，375(16):1552-1565. DOI： 10.1056/NEJMra1510030 .
返回引文位置Google Scholar
百度学术
万方数据
[25]
Douglas RS , Afifiyan NF , Hwang CJ ，et al. Increased generation of fibrocytes in thyroid-associated ophthalmopathy[J]．J Clin Endocrinol Metab， 2010，95(1):430-438. DOI： 10.1210/jc.2009-1614 .
返回引文位置Google Scholar
百度学术
万方数据
[26]
Smith TJ , Hegedüs L , Douglas RS . Role of insulin-like growth factor-1 (IGF-1) pathway in the pathogenesis of Graves' orbitopathy[J]．Best Pract Res Clin Endocrinol Metab， 2012，26(3):291-302. DOI： 10.1016/j.beem.2011.10.002 .
返回引文位置Google Scholar
百度学术
万方数据
[27]
Fernando R , Atkins S , Raychaudhuri N ，et al. Human fibrocytes coexpress thyroglobulin and thyrotropin receptor[J]．Proc Natl Acad Sci U S A， 2012，109(19):7427-7432. DOI： 10.1073/pnas.1202064109 .
返回引文位置Google Scholar
百度学术
万方数据
[28]
Fernando R , Lu Y , Atkins SJ ，et al. Expression of thyrotropin receptor，thyroglobulin，sodium-iodide symporter，and thyroperoxidase by fibrocytes depends on AIRE[J/OL]．J Clin Endocrinol Metab， 2014，99(7):E1236-1244[2020-08-10]. http:// pubmed.ncbi.nlm.nih.gov/24708100/ DOI： 10.1210/jc.2013-4271 .
返回引文位置Google Scholar
百度学术
万方数据
[29]
Lu Y , Atkins SJ , Fernando R ，et al. CD34- orbital fibroblasts from patients with thyroid-associated ophthalmopathy modulate TNF-α expression in CD34＋ fibroblasts and fibrocytes[J]．Invest Ophthalmol Vis Sci， 2018，59(6):2615-2622. DOI： 10.1167/iovs.18-23951 .
返回引文位置Google Scholar
百度学术
万方数据
[30]
Smith TJ . Potential roles of CD34＋ fibrocytes masquerading as orbital fibroblasts in thyroid-associated ophthalmopathy[J]．J Clin Endocrinol Metab， 2019，104(2):581-594. DOI： 10.1210/jc.2018-01493 .
返回引文位置Google Scholar
百度学术
万方数据
[31]
Fang S , Huang Y , Liu X ，et al. Interaction between CCR6＋ Th17 cells and CD34＋ fibrocytes promotes inflammation：implications in Graves' orbitopathy in chinese population[J]．Invest Ophthalmol Vis Sci， 2018，59(6):2604-2614. DOI： 10.1167/iovs.18-24008 .
返回引文位置Google Scholar
百度学术
万方数据
[32]
Wu T , Mester T , Gupta S ，et al. Thyrotropin and CD40L stimulate Interleukin-12 expression in fibrocytes：implications for pathogenesis of thyroid-associated ophthalmopathy[J]．Thyroid， 2016，26(12):1768-1777. DOI： 10.1089/thy.2016.0243 .
返回引文位置Google Scholar
百度学术
万方数据
[33]
Johnson KT , Wiesweg B , Schott M ，et al. Examination of orbital tissues in murine models of Graves' disease reveals expression of UCP-1 and the TSHR in retrobulbar adipose tissues[J]．Horm Metab Res， 2013，45(6):401-407. DOI： 10.1055/s-0032-1333224 .
返回引文位置Google Scholar
百度学术
万方数据
[34]
Taylor PN , Zhang L , Lee R ，et al. New insights into the pathogenesis and nonsurgical management of Graves orbitopathy[J]．Nat Rev Endocrinol， 2020，16(2):104-116. DOI： 10.1038/s41574-019-0305-4 .
返回引文位置Google Scholar
百度学术
万方数据
[35]
Genere N , Stan MN . Current and emerging treatment strategies for Graves' orbitopathy[J]．Drugs， 2019，79(2):109-124. DOI： 10.1007/s40265-018-1045-9 .
返回引文位置Google Scholar
百度学术
万方数据
[36]
Smith TJ , Kahaly GJ , Ezra DG ，et al. Teprotumumab for thyroid-associated ophthalmopathy[J]．N Engl J Med， 2017，376(18):1748-1761. DOI： 10.1056/NEJMoa1614949 .
返回引文位置Google Scholar
百度学术
万方数据
[37]
Douglas RS , Kahaly GJ , Patel A ，et al. Teprotumumab for the treatment of active thyroid eye disease[J]．N Engl J Med， 2020，382(4):341-352. DOI： 10.1056/NEJMoa1910434 .
返回引文位置Google Scholar
百度学术
万方数据
[38]
Savino G , Mandarà E , Gari M ，et al. Intraorbital injection of rituximab versus high dose of systemic glucocorticoids in the treatment of thyroid-associated orbitopathy[J]．Endocrine， 2015，48(1):241-247. DOI： 10.1007/s12020-014-0283-1 .
返回引文位置Google Scholar
百度学术
万方数据
[39]
Salvi M , Vannucchi G , Currò N ，et al. Efficacy of B-cell targeted therapy with rituximab in patients with active moderate to severe Graves' orbitopathy：a randomized controlled study[J]．J Clin Endocrinol Metab， 2015，100(2):422-431. DOI： 10.1210/jc.2014-3014 .
返回引文位置Google Scholar
百度学术
万方数据
[40]
Stan MN , Garrity JA , Carranza Leon BG ，et al. Randomized controlled trial of rituximab in patients with Graves' orbitopathy[J]．J Clin Endocrinol Metab， 2015，100(2):432-441. DOI： 10.1210/jc.2014-2572 .
返回引文位置Google Scholar
百度学术
万方数据
[41]
Chen G , Ding Y , Li Q ，et al. Defective regulatory B cells are associated with thyroid associated ophthalmopathy[J]．J Clin Endocrinol Metab， 2019，104(9):4067-4077. DOI： 10.1210/jc.2018-01812 .
返回引文位置Google Scholar
百度学术
万方数据
备注信息
A
范先群，Email： mocdef.6ab21nuqnaixnafrd
B
所有作者均声明不存在任何利益冲突
C
国家自然科学基金项目 (81930024、81770974)
上海市科学技术委员会项目 (17DZ2260100)
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