Transcriptome analysis of orbital tissue in thyroid eye disease uncovers key pathogenic mediators.

This study employed RNA sequencing and bioinformatics to identify differentially expressed genes (DEGs) and signaling pathways in thyroid eye disease (TED). Orbital adipose tissues from TED patients and normal controls were sequenced, followed by DEG screening. Primary cultured orbital fibroblasts were used to validate highly expressed DEGs via qRT-PCR. We observed significant upregulation of genes involved in adipogenesis (e.g., ACSL5), muscle fiber formation/contraction (e.g., TNNT1), and nerve injury (e.g., NEFM) in TED. qRT-PCR confirmed elevated expression of IL-6, COL1A1, PPARγ, NEFM, ACSL5, and TNNT1 in TED fibroblasts. Enrichment analysis revealed 20 significantly altered biological processes, including triglyceride biosynthesis and muscle filament sliding. Upregulated DEGs were primarily associated with the PPAR, AMPK, and adipocytokine signaling pathways. Our findings identify ACSL5, TNNT1, and NEFM as key mediators in TED pathogenesis, contributing to adipogenesis, muscle thickening, and nerve injury, respectively. The PPARγ-ACSL5 pathway is implicated in orbital adipogenesis, suggesting potential therapeutic targets for TED.