The Role of Pyroptosis in Age-Related Cataracts: Insights from Gene Expression Analysis

Abstract

Background: Understanding cataract development is essential for addressing its impact on global healthcare systems. Pyroptosis has been implicated in cataract formation, but the underlying mechanisms remain poorly understood.

Objectives: While pyroptosis is thought to contribute to cataract development, the exact mechanisms are not fully understood. This study aimed to investigate the role of pyroptosis in the progression of age-related cataract formation.

Methods: The GSE161701 dataset was retrieved from the Gene Expression Omnibus (GEO) database to compare lens tissue samples from 12 distinct chips. These samples were obtained via high-throughput sequencing of human lens epithelial cells, specifically wild-type (WT) HLE-B3 cells and Atg7 knockout (Atg7KO) HLE-B3 cells, treated with or without 200 μM H2O2 for 12 hours. The limma package in R was used to identify significantly differentially expressed genes (DEGs). Gene Ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Reactome pathway analysis were conducted on the identified DEGs using Metascape. Additionally, the STRING online tool and Cytoscape software were employed to construct the protein-protein interaction (PPI) network.

Results: A total of 6,156 differentially expressed genes (DEGs) were identified, including 5,196 up-regulated and 960 down-regulated genes. Previous studies have highlighted 55 genes associated with pyroptosis. Gene Set Enrichment Analysis (GSEA) indicated that most up-regulated genes and pathways were related to IL18, IL2, IL4, Notch, MAPK signaling pathways, various cytokines, and the inflammatory response. In contrast, down-regulated genes and pathways were primarily linked to FOXM1 and PLK1. A further search in the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases identified DEGs related to pyroptosis. The PPI network analysis revealed that IL6, TNF, IL1A, IL1β, and NLRP3 had high connectivity, suggesting potential interactions and mutual influence among these proteins.

Conclusion: Pyroptosis significantly affects the expression of inflammatory cytokines in human lens epithelial cells, particularly interleukin 6 (IL-6), tumor necrosis factor (TNF), interleukin 1 alpha (IL-1A), interleukin 1 beta (IL-1β), and NLRP3. The regulation of these cytokines may be crucial in the pathogenesis of age-related cataracts, presenting potential therapeutic targets for intervention.