Antioxidant Therapy in Graves’ Orbitopathy

Lanzolla, Giulia; Marcocci, Claudio; Marinò, Michele

doi:10.3389/fendo.2020.608733

Cited by 10 publications

(6 citation statements)

References 58 publications

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“…Ma and his colleagues identified ferroptosis resistance in OFs cultured from TAO patients. These cells presented with higher viability than OFs obtained from healthy individuals after cystine deprivation, which is a frequently used method for stimulating the genesis of ferroptosis ( Lanzolla et al, 2020 ). In research on aging diseases, senescence was shown to make cells extremely resistant to ferroptosis due to the accumulation of intracellular iron ( Masaldan et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of ferroptosis-related genes and immune cell infiltration in thyroid associated ophthalmopathy

et al. 2023

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Thyroid associated ophthalmopathy (TAO) is an orbital autoimmune inflammatory disease that is commonly associated with thyroid dysfunction. Although the etiology of TAO is unclear, ROS accumulation and oxidative stress have been closely linked to the pathogenesis of TAO. Ferroptosis is an iron-dependent programmed cell death characterized by intracellular labile iron levels, excessive accumulation of reactive oxygen species (ROS) and lipid peroxidation. Currently, there are few reports regarding the role of ferroptosis in TAO. This article aimed to identify ferroptosis-related genes (FRGs) with diagnostic and therapeutic potential in TAO and explore their relationship with immune cells and lncRNAs. GSE58331 was downloaded from Gene Expression Omnibus (GEO) database. A total of 162 DEGs were identified between 27 TAO samples and 22 health samples from GSE58331, among which six FRGs (CYBB, CTSB, SLC38A1, TLR4, PEX3, and ABCC1) were obtained. The AUC of SLC38A1, TLR4, PEX3 in lacrimal gland tissues was greater than 80 which suggested high diagnostic value in TAO. The result of immune cell infiltrate analysis indicated increased infiltration of monocytes (p < 0.001), macrophages M0(p = 0.039), mast cells activated (p = 0.008), and neutrophils (p = 0.045) in orbital tissues from TAO patients. Meanwhile, mast cells resting (p = 0.043) and macrophages M2 (p = 0.02) showed reduced infiltration in TAO samples. There were no gender differences in immune cell infiltration in the TAO patients. Two differentially expressed lncRNAs, LINC01140 and ZFHX4-AS1, in TAO groups were identified as ferroptosis-related lncRNAs. CYBB-LINC01140-TLR4, CYBB- LINC01140- SLC38A1, TLR4- LINC01140- SLC38A1, and CTSB- ZFHX4-AS1- CYBB may be potential RNA regulatory pathways in TAO. Targeted drugs and transcription factors for differential expressed FRGs were also screened out in our study. In vitro, experiments revealed that CTSB, PEX3, ABCC1 and ZFHX4-AS1(lncRNA) were differentially expressed in orbital fibroblasts (OFs) between TAO groups and healthy controls at the transcriptional level.

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Section: Discussionmentioning

confidence: 99%

Identification and validation of ferroptosis-related genes and immune cell infiltration in thyroid associated ophthalmopathy

et al. 2023

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“…Multiple potential antioxidants have been described in GO, including selenium, pentoxifylline, quercetin, enalapril, allopurinol, nicotinamide, vitamin C, N-acetylcysteine, melatonin, β-carotene, and statins [ 80 , 81 , 82 ]. A recent systematic review [ 80 ] included four clinical and ten in vitro studies from 1993 to 2018, and demonstrated that selenium was the only antioxidant based on in vitro and randomized controlled trial studies.…”

Section: Treatment For Tissue Remodeling In 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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“…The role of oxidative stress and selenium deficit has been also described. [21][22][23] A prospective observational study performed by EUGOGO to construct a predictive score for the occurrence and progression of GO in patients with recent onset GD has been recently performed. 24 Using mixed-effect logistic regression analysis, 4 determinants were identified, namely CAS, Thyroid-stimulating hormone (TSH)-binding inhibitor immunoglobulins, smoking, and longer duration of hyperthyroid symptoms.…”

Section: Go: Standard Treatment and Future Perspectivesmentioning

confidence: 99%

Statins in Graves Orbitopathy: A New Therapeutic Tool

Lanzolla,

Comi,

Cosentino

et al. 2023

Ophthalmic Plastic &Amp; Reconstructive Surgery

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Purpose: Graves orbitopathy (GO) is the most common extrathyroidal manifestation of Graves disease. Although its pathogenesis is not fully elucidated, GO is commonly considered an autoimmune disease due to loss of self-tolerance against autoantigens shared by thyroid epithelial cells and orbital fibroblasts. High-dose intravenous glucocorticoids (ivGCs) are the most used treatment for moderate-to-severe, active GO, but the addition of other immunomodulating treatments can improve the efficacy of ivGCs. Among the various risk factors that can affect the occurrence of GO, cholesterol may be worthy of interest. Since 2015 the role of cholesterol and cholesterol-lowering medications has been investigated. The purpose of this review is to discuss this topic, thereby offering new therapeutic opportunities for patients with GO. Methods: We searched PubMed for studies published between January 1, 1980 and June 1, 2023, using the search terms “Graves orbitopathy,” “thyroid eye disease,” “Graves ophthalmopathy,” “thyroid ophthalmopathy,” “thyroid-associated ophthalmopathy,” “endocrine ophthalmopathy,” “cholesterol,” “lipids,” “statins,” “low-density lipoprotein,” “atorvastatin,” and “cholesterol-lowering drugs.” Only English-language articles were included. Results: A correlation between low-density lipoprotein cholesterol and the risk of GO development has been reported. Furthermore, low-density lipoprotein cholesterol has been proposed as a risk factor that can affect the course of GO and the response to ivGCs. The protective role of cholesterol-lowering medications in preventing GO has been also investigated. Statin treatment was found to have potential benefits in reducing the risk of GO in patients with Graves disease. Given these findings, measurement of low-density lipoprotein cholesterol and treatment of hypercholesterolemia in patients with moderate-to-severe, active GO may be considered before starting ivGCs administration. Recently, a randomized clinical trial aimed at investigating the effects of statins in GO suggested that the addition of oral atorvastatin to ivGCs improves the overall outcome of moderate-to-severe, active GO in hypercholesterolemic patients given ivGCs. Conclusions: Overall, statins seem to have a preventive and therapeutic role in moderate-to-severe active GO. Their efficacy can be related to cholesterol-lowering activity, pleiotropic actions, and interaction with methylprednisolone.

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Antioxidant Therapy in Graves’ Orbitopathy

Cited by 10 publications

References 58 publications

Identification and validation of ferroptosis-related genes and immune cell infiltration in thyroid associated ophthalmopathy

Identification and validation of ferroptosis-related genes and immune cell infiltration in thyroid associated ophthalmopathy

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

Statins in Graves Orbitopathy: A New Therapeutic Tool

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