Purpose

To investigate whether orbital adipose tissue derived miRNA profiles differ between Graves’ ophthalmopathy (GO) and healthy controls and to explore their potential role in disease activity or asymmetry.

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Methods

Twelve orbital adipose tissue samples were analyzed: active GO (n=3), asymmetric inactive GO (more affected eyes, n=3; less affected eyes, n=3), and healthy controls (n=3). Total RNA was isolated, and miRNA profiles were obtained using next-generation sequencing. Differential expression analysis was performed, miRNA profiles were compared between groups. P values were adjusted using the Benjamini-Hochberg method to control the false discovery rate (FDR).

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Results

High quality sequencing data were obtained across all groups. Principal component analysis revealed distinct clustering of active GO versus inactive GO and controls. In active GO, relative to controls, myomiRs (miR-1, miR-133, miR-206), miR-196, and miR-9 were downregulated (p≤0.05), whereas the miR-200 family (miR-141, miR-200a/b/c), miR-146b, and miR-205 were upregulated (p≤0.05). No statistically significant differences were detected between inactive GO subgroups or between active and inactive GO.

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Conclusion

Active GO exhibits a distinct miRNA expression profile, including members of the miR-200 family and myomiRs, which are implicated in fibrosis, adipogenesis, myogenesis, and IGF-1 signaling pathways. The absence of differences between active and inactive GO suggests that molecular activity may persist despite clinical inactivity. The lack of differences between eyes in asymmetric GO suggests a role for local rather than systemic factors. These findings indicate that miRNA dysregulation in orbital adipose tissue may contribute to disease activity and highlight miRNAs as potential biomarkers and therapeutic targets in Graves’ ophthalmopathy.

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Additional Authors

First name	Last name	Base Hospital / Institution
Volkan	Dericioglu	Marmara University Faculty of Medicine Department of Ophthalmology
Tunc	Akkoc	Marmara University Faculty of Medicine Department of Immunology
Sabriye Senem	Kilic	Marmara University Faculty of Medicine Department of Immunology

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