Anatomical Region-Specific Transcriptomic Signatures and the Role of Epithelial Cells in Pterygium Inflammation: A Multi-Omics Analysis.

Purpose: This study aims to understand the differences in cellular and molecular patterns between the Main and Accessory (Acc) regions of pterygium tissue, with a focus on inflammation and mitochondrial energy metabolism. Methods: We collected bulk RNA sequencing (RNA-seq) data from six pterygium patients and single-cell RNA-seq data from two pterygium patients. Subsequently, we investigated pathway enrichment, pathway correlation, differential gene expression, protein-protein interactions, and cell-cell communication in pterygium. Results: Bulk RNA-seq analysis revealed distinct expression patterns in the Acc group compared to the Main and control groups. This finding suggested the need to separate the Main and Acc regions within pterygium samples and use single-cell data to understand differences between the Main and control groups that bulk data could not capture. The single-cell data identified a cluster of epithelial cells containing only pterygium samples, which contributed significantly to the ANGPTL, IL1, and KLK signaling networks. Cells involved in inflammatory pathways associated with the integrated stress response and the renin-angiotensin-aldosterone system, both of which exhibited high correlations with energy metabolism-associated pathways, were significantly upregulated. Additionally, expression changes in multiple proinflammatory, antioxidant, and immune-associated genes were identified. Conclusions: The distinctions between the Main and Acc groups suggest the necessity of distinguishing anatomical regions in future pterygium studies. Additionally, the pivotal role of epithelial cells from the Main group in the inflammation of pterygium indicates a potential clinical approach for managing the disease. Translational Relevance: This study aims to identify apex-specific biomarkers of pterygium for a more efficient diagnosis and treatment.