Current and promising therapies based on the pathogenesis of Graves’ ophthalmopathy

Abstract

Graves’ ophthalmopathy (GO) is a hyperthyroidism-related and immune-mediated disease that poses a significant threat to human health. The pathogenesis of GO primarily involves T cells, B cells, and fibroblasts, suggesting a pivotal role for the thyrotropin-antibody-immunocyte-fibroblast axis. Traditional treatment approaches for Graves’ disease (GD) or GO encompass antithyroid drugs (ATDs), radioactive iodine, and beta-blockers. However, despite decades of treatment, there has been limited improvement in the global incidence of GO. In recent years, promising therapies, including immunotherapy, have emerged as leading contenders, demonstrating substantial benefits in clinical trials by inhibiting the activation of immune cells like Th1 and B cells. Furthermore, the impact of diet, gut microbiota, and metabolites on GO regulation has been recognized, suggesting the potential of non-pharmaceutical interventions. Moreover, as traditional Chinese medicine (TCM) components have been extensively explored and have shown effective results in treating autoimmune diseases, remarkable progress has been achieved in managing GO with TCM. In this review, we elucidate the pathogenesis of GO, summarize current and prospective therapies for GO, and delve into the mechanisms and prospects of TCM in its treatment.

Identification of potential immunotherapeutic targets and prognostic biomarkers in Graves' disease using weighted gene co-expression network analysis

“…Further analysis through KEGG pathways identified significant associations between dark-red module genes and pathways integral to neuroactive ligand-respecter interactions and DNA binding transcription factor activity within purinergic signaling [ 50 ]. Recognized for their roles in regulating immune responses and inflammation, these pathways have implications for various autoimmune disorders, including GD [ 51 ]. Notably, our study unveiled pathways associated with cognitive impairment, suggesting a potential link between the molecular mechanisms identified in GD and observed cognitive dysfunction.…”

“…Notably, our study unveiled pathways associated with cognitive impairment, suggesting a potential link between the molecular mechanisms identified in GD and observed cognitive dysfunction. The integrated analysis of purinergic signaling pathways, neuroactive ligand-respecter interaction, and DNA binding transcription factor activity offered a comprehensive view of their interplay in contributing to GD pathophysiology [ [51] , [52] , [53] ]. Moreover, our investigation revealed the paramount role of the neuroactive ligand-respecter interaction pathway in producing thyroid-stimulating immunoglobulins in the GD [ 50 ].…”

Thyroid-associated ophthalmopathy: the role of oxidative stress

“…Increased ROS production and compromised antioxidant capacity can lead to cellular damage and dysfunction in TAO. Understanding these mechanisms requires exploring oxidative stress at the organelle level and its impact on inflammation and fibrosis, critical components in TAO pathophysiology ( 45 , 46 ). Oxidative stress perpetuates inflammation, exacerbating tissue damage in a vicious cycle.…”