Research progress on the pathogenesis of Graves’ ophthalmopathy: Based on immunity, noncoding RNA and exosomes

Zheng, Jiang Yu; Duan, Honghong; You, Sufang; Liu, Bo; Chen, Yuping; Huang, Huibin

doi:10.3389/fimmu.2022.952954

Cited by 9 publications

(5 citation statements)

References 96 publications

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“…Diplopia and compressive optic neuropathy are significant symptoms of TED that occur because of extraocular muscle enlargement. TED is thought to be an autoimmune disorder in which the autoantigen acts on the TSH receptors of CD34-positive fibroblasts in the orbital tissue [ 17 – 20 ]. Activated fibroblasts and lymphocytes infiltrating the orbit produce cytokines.…”

Section: Discussionmentioning

confidence: 99%

Correlation between extraocular muscle enlargement and thyroid autoantibodies in thyroid eye disease

Koizumi,

Tanaka,

Umeda

et al. 2024

Jpn J Ophthalmol

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Purpose This study aimed to investigate the factors affecting extraocular muscle enlargement in thyroid eye disease (TED). Study design Retrospective study. Methods The thyroid-stimulating hormone (TSH) receptor antibody (TRAb), thyroid-stimulating antibody (TSAb), antithyroid peroxidase antibody (ATPO), and antithyroglobulin antibody (ATG) levels in patients diagnosed with TED who underwent orbital magnetic resonance imaging were assessed. The control group comprised the contralateral eye of patients who underwent orbital magnetic resonance imaging (MRI) for unilateral eyelid tumors or orbital disease. The thickness of the bilateral rectus muscles and superior oblique muscles was measured on orbital MRI. Muscle enlargement was classified as unilateral/bilateral and symmetric/asymmetric. The effects of age, sex, smoking history, TSH, thyroid hormone, and thyroid autoantibodies on the muscle thickness and number of enlarged muscles were assessed by use of simple and multiple regression analyses. Results The TED and control groups comprised 41 and 44 cases, respectively. The positivity rate of TSAb in patients with TED was 92.7% higher than that of the other autoantibodies. Muscle enlargement was observed in 29 of the 41 cases (70.7%). Older age and higher TSAb levels were identified as significant factors affecting the total muscle thickness and number of enlarged muscles. Bilateral muscle enlargement and asymmetrical muscle enlargement were observed in 17 (58.6%) and 23 (79.3%) of the 29 cases, respectively. The TSAb levels and age had no significant effect on the type of muscle enlargement. Conclusions TSAb showed significant associations with extraocular muscle enlargement. Measurement of TSAb, rather than of TRAb, may be more useful for diagnosing extraocular muscle enlargement in patients with TED.

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Section: Discussionmentioning

confidence: 99%

Correlation between extraocular muscle enlargement and thyroid autoantibodies in thyroid eye disease

Koizumi,

Tanaka,

Umeda

et al. 2024

Jpn J Ophthalmol

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“…With advanced gene sequencing technology, the epigenetics in the pathogenesis of GO has been studied in recent years [ 53 , 54 ]. Although the research is still in its infancy, histone modification, DNA methylation and non-coding RNAs bring emerging insights and novel potential therapeutic strategies.…”

Section: Epigenetics and The Gut Microbiome In The Ecm Of Gomentioning

confidence: 99%

The Role of Fibrogenesis and Extracellular Matrix Proteins in the Pathogenesis of Graves’ Ophthalmopathy

Chiu,

Wu,

Tsai

2024

IJMS

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Graves’ ophthalmopathy (GO), or thyroid eye disease (TED), is the most frequent extrathyroidal manifestation of Graves’ disease (GD). Inflammation and subsequent aberrant tissue remodeling with fibrosis are important pathogenesis. There are many proposed mechanisms and molecular pathways contributing to tissue remodeling and fibrosis in GO, including adipogenesis, fibroblast proliferation and myofibroblasts differentiation, oxidative stress, endoplasmic reticulum (ER) stress, hyaluronan (HA) and glycosaminoglycans (GAGs) accumulation in the extracellular matrix (ECM) and new concepts of epigenetics modification, such as histone modification, DNA methylation, non-coding RNAs, and gut microbiome. This review summarizes the current understanding of ECM proteins and associated tissue remodeling in the pathogenesis and potential mediators for the treatment of GO.

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“…Both diseases may share a common mechanism, and the TSHR autoantigen plays a role [ 9 , 68 ]. Some studies report a correlation between ocular changes and the level of TSHR-stimulating antibodies (i.e., thyroid-stimulating immunoglobulins, TSIs) [ 14 , 15 ].…”

Section: Pathogenesismentioning

confidence: 99%

“…Similar to GD, TED is caused by an autoimmune response. The pathophysiology underlying TED is complex, with key factors being the infiltration of activated T and B lymphocytes, activation of orbital fibroblasts (OFs), and the presence of autoantibodies targeting a common autoantigen (i.e., TSHR) expressed in thyroid and orbital tissues [ 6 , 7 , 9 , 10 , 11 , 12 , 13 , 14 ]. In TED, TSHR receptor antibodies (TRABs) and antibodies to insulin-like growth factor 1 receptor (anti-IGF-1R) interact with OFs.…”

Section: Introductionmentioning

confidence: 99%

Immunological Processes in the Orbit and Indications for Current and Potential Drug Targets

Cieplińska,

Niedziela,

Kowalska

2023

JCM

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Thyroid eye disease (TED) is an extrathyroidal manifestation of Graves’ disease (GD). Similar to GD, TED is caused by an autoimmune response. TED is an autoimmune inflammatory disorder of the orbit and periorbital tissues, characterized by upper eyelid retraction, swelling, redness, conjunctivitis, and bulging eyes. The pathophysiology of TED is complex, with the infiltration of activated T lymphocytes and activation of orbital fibroblasts (OFs) and autoantibodies against the common autoantigen of thyroid and orbital tissues. Better understanding of the multifactorial pathogenesis of TED contributes to the development of more effective therapies. In this review, we present current and potential drug targets. The ideal treatment should slow progression of the disease with as little interference with patient immunity as possible. In the future, TED treatment will target the immune mechanism involved in the disease and will be based on a strategy of restoring tolerance to autoantigens.

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Research progress on the pathogenesis of Graves’ ophthalmopathy: Based on immunity, noncoding RNA and exosomes

Cited by 9 publications

References 96 publications

Correlation between extraocular muscle enlargement and thyroid autoantibodies in thyroid eye disease

Correlation between extraocular muscle enlargement and thyroid autoantibodies in thyroid eye disease

The Role of Fibrogenesis and Extracellular Matrix Proteins in the Pathogenesis of Graves’ Ophthalmopathy

Immunological Processes in the Orbit and Indications for Current and Potential Drug Targets

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