ORF18-01 - The Flavanol Gallocatechin as a Novel Therapeutic Candidate for Thyroid Eye Disease by Mitigating Pathological Remodeling in Orbital fibroblasts

Purpose: Thyroid eye disease (TED) is a refractory disease, pathologically characterized by excessive proliferation, adipogenesis, and hyaluronan production in orbital fibroblasts (OFs). Here we aim to investigate whether gallocatechin (GC), the natural flavanol from plants with antioxidant and anti-inflammatory properties, has the potential to attenuate the pathological activation of OFs.

Methods: Primary OFs, isolated from patients with or without TED, were treated with varying concentrations of GC. Cell proliferation was assessed using EdU incorporation assays. Intracellular lipid accumulation was evaluated by Oil Red O staining and Western blot analysis. Hyaluronan production was determined by ELISA. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were performed using RNA sequencing to illustrate the underlying mechanisms.

Results: GC significantly reduced lipid droplet accumulation and expression of adipogenic markers (FASN, PELN1 and FABP4) of TED-OFs in a dose-dependent manner without inducing cytotoxicity. Meanwhile, GC inhibited both proliferation and hyaluronan secretion in TED-OFs. Transcriptome analysis identified 215 differentially expressed genes (DEGs), mainly enriched in biological processes related to oxidative stress, immune/inflammatory responses, and vesicle-mediated secretion. Key genes related to adipogenesis, immune responses, and secretion were down-regulated. Moreover, CREB1 and SERPINA1 were identified as potential molecular targets mediating the effects of GC.

Conclusions: GC alleviates pathological remodeling of OFs in TED by inhibiting cell proliferation, adipogenesis, and hyaluronan production, likely benefit by its potent anti-inflammation and antioxidant properties. These results demonstrate that GC is a prospective therapeutic candidate for TED with safe and cost-effective properties.

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