Differences in gene expression between the primary and secondary inferior oblique overaction.

Background: This study sought to define different adaptive changes in the molecular levels of the overacting inferior oblique muscle in primary and secondary inferior oblique overaction. Methods: The inferior oblique muscles of patients with congenital superior oblique palsy (SOP) and those of patients with congenital esotropia were collected during surgery. RNA-seq technology was performed to detect the differentially expressed genes (DEGs) between the two groups. A comprehensive analysis of the gene expression profiles was then conducted, including the identification of DEGs, a Gene Ontology (GO) analysis, and a gene set enrichment analysis (GSEA). Finally, a protein-protein interaction (PPI) network was constructed with Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and Cytoscape software. Results: We identified 221 DEGs, of which 104 were significantly upregulated and 117 were downregulated in the SOP group. Additionally, several isoforms of the myosin heavy chain (MyHC) gene were found to be significantly and differentially expressed in the SOP group, including 3 upregulated fast-twitch MyHC isoforms (i.e., Conclusions: Our findings provide insights into the different molecular changes of inferior oblique muscle overaction secondary to SOP and suggest the potential pathological mechanisms of inferior oblique overaction (IOOA) in SOP. The results suggest that upregulated fast-twitch MyHC isoforms and downregulated slow-twitch MyHC isoform in SOP may contribute to the increased force of its inferior oblique muscle.