Thyroid-associated ophthalmopathy is a typical autoimmune disease of orbital tissues. Alternative splicing significantly influences many diseases progression, including cancer, age-related macular degeneration, and multiple sclerosis, by modulating the expression of transcripts. However, its role in thyroid-associated ophthalmopathy is still unclear. In this study, differential expression transcripts and differential alternative splicing genes in orbital adipose/connective tissues of thyroid-associated ophthalmopathy patients were detected using RNA sequencing, Cuffdiff, and replicate multivariate analysis of transcript splicing. Three thousand ninety six differential expression transcripts and 2355 differential alternative splicing genes were screened out, while functional enrichment analysis indicated that differential expression transcript and differential alternative splicing genes were associated with immune modulation, extracellular matrix remodeling, and adipogenesis. The expression of the SORBS1, SEPT2, COL12A1, and VCAN gene transcripts was verified by qRT-PCR. In conclusion, prevalent alternative splicing is involved in the disease development in thyroid-associated ophthalmopathy. More attention should be paid to the mechanism of alternative splicing to explore more potential therapeutic targets in thyroid-associated ophthalmopathy.
Keywords: Thyroid-associated ophthalmopathy; adipogenesis; adipose/connective tissue; alternative splicing; rMATS.