Immunosuppressive Pulse Therapy Alleviates Ocular Surface Damage in Thyroid-Associated Ophthalmopathy by Reversing FGA Deficiency Subsequently Modulating Complement and Coagulation Cascade Signaling to Suppress Orbital Fibroblast Pathology

BACKGROUND: Thyroid-associated ophthalmopathy (TAO)is a common autoimmune inflammatory disorder that compromises visual function and quality of life. It is characterized by orbital tissue inflammation and ocular surface injury. Although immunosuppressive pulse therapy has shown clinical efficacy, its underlying molecular mechanisms remain incompletely understood. METHODS: Tear samples were collected from 30 healthy controls and 30 patients with TAO before and after immunosuppressive pulse therapy. Proteomic profiling was performed using label-free quantitative liquid chromatography - tandem mass spectrometry (LC-MS/MS), and key proteins involved in FGA expression and complement-coagulation cascade signaling were validated by ELISA. Primary orbital fibroblasts (OFs) were isolated from TAO patients and subjected to FGA overexpression and immunosuppressant treatment. Fibrosis and adipogenic differentiation were assessed using a multidimensional approach, including CCK-8 assay, flow cytometry, Oil Red O staining, qRT-PCR, and Western blotting. RESULTS: Immunosuppressive pulse therapy significantly alleviates ocular surface injury in TAO patients, primarily through FGA-mediated regulation of the complement and coagulation cascade pathway. Our findings identify FGA as a promising therapeutic target in TAO. Restoration of FGA expression synergizes with immunosuppressive therapy, highlighting a potential combinatory treatment strategy. CONCLUSION: FGA represents a potential therapeutic target for TAO. Enhancing FGA expression may augment the efficacy of immunosuppressive therapythrough synergistic modulationof inflammatory and fibrotic pathways. CLINICAL TRIAL NUMBER: Not applicable.