The Role of Oxidative Stress and Therapeutic Potential of Antioxidants in Graves’ Ophthalmopathy

Abstract

Graves’ ophthalmopathy (GO) is the most common extrathyroidal manifestation of Graves’ disease. It is characterized initially by an inflammatory process, followed by tissue remodeling and fibrosis, leading to proptosis, exposure keratopathy, ocular motility limitation, and compressive optic neuropathy. The pathogenic mechanism is complex and multifactorial. Accumulating evidence suggests the involvement of oxidative stress in the pathogenesis of GO. Cigarette smoking, a major risk factor for GO, has been shown to induce reactive oxygen species (ROS) generation and oxidative damage in GO orbital fibroblasts. In addition, an elevation in ROS and antioxidant enzymes is observed in tears, blood, and urine, as well as orbital fibroadipose tissues and fibroblasts from GO patients. In vitro and in vivo studies have examined the efficacy of various antioxidant supplements for GO. These findings suggest a therapeutic role of antioxidants in GO patients. This review summarizes the current understanding of oxidative stress in the pathogenesis and potential antioxidants for the treatment of GO.

Novel Insight into Non-Genetic Risk Factors of Graves’ Orbitopathy

“…Reactive oxygen species (ROS) were demonstrated to play a role in GO development. They stimulate orbital fibroblast proliferation, synthesis of glycosaminoglycans and inflammatory mediators [ 13 ]. Increased concentrations of ROS were found not only in blood, but also in the urine of GO patients [ 13 ].…”

Current concepts regarding Graves’ orbitopathy

“…Reactive oxygen species stimulate orbital fibroblast proliferation, glycosaminoglycan synthesis, and upregulation of inflammatory and noninflammatory mediators [104] (Table 2). Increased concentrations of reactive oxygen species have been reported in the blood, tears, and urine of GO patients [104]. Selenium is a trace element relevant for the thyroid because selenocysteine is incorporated into selenoproteins such as iodothyronine deiodinases—involved in thyroid hormone deiodination—or thioredoxin reductase and glutathione peroxidase [105], which exert antioxidant effects [106].…”

“…Increased oxidative stress is found in patients with Graves’ disease and GO [103]. Reactive oxygen species stimulate orbital fibroblast proliferation, glycosaminoglycan synthesis, and upregulation of inflammatory and noninflammatory mediators [104] (Table 2). Increased concentrations of reactive oxygen species have been reported in the blood, tears, and urine of GO patients [104].…”

“…tears, and urine of GO patients Hou et al[104] Hypercholesterolemia High total and LDL cholesterol associated with the presence of GO Sabini et al[109] Reduced risk of GO in patients receiving statin treatment Stein et al[111] Nilsson et al[112] Increased effectiveness of ivGCs in patients treated with atorvastatin Lanzolla et al[114] Abbreviations: ivGCs, intravenous glucocorticoids; LDL, low-density lipoprotein; RAI, radioactive iodine; TSHR-Ab, TSH receptor antibodies.…”

Tears as a Source of Biomarkers in the Diagnosis of Graves’ Orbitopathy

“…Oxidative stress is represented by excess reactive oxygen species (ROS), which disturb the intracellular redox state, leading to peroxide and free radical accumulation and subsequent damage to proteins, lipids, and DNA in cells. The involvement of oxidative stress in the pathogenesis of GD and GO has been examined throughout the years [ 44 ]. Various markers of oxidative damage have been identified.…”