Integrated Profiling of Extracellular Vesicle microRNA Impact on Trabecular Meshwork mRNA Expression: Insights From Microarray Analysis.

PURPOSE: Extracellular vesicles (EVs) secreted by non-pigmented ciliary epithelial (NPCE) cells under oxidative stress may contribute to primary open-angle glaucoma (POAG) pathogenesis by altering gene expression in human trabecular meshwork (HTM) cells. This study investigated the impact of microRNAs (miRNAs) carried by NPCE-derived EVs on HTM cell gene expression under oxidative stress conditions. METHODS: NPCE cells were exposed to oxidative stress, and EVs were isolated from control and stressed cells. HTM cells were treated with these EVs, followed by microarray analysis to identify differentially expressed miRNAs in EVs and messenger RNAs (mRNAs) in HTM cells. Bioinformatics analysis was used to explore miRNA-mRNA interactions, enriched Gene Ontology (GO) terms, and miRNA-mRNA-GO networks. RESULTS: The study identified 54 differentially expressed miRNAs in stressed NPCE EVs. In HTM cells treated with stressed NPCE EVs, 88 genes were upregulated and 58 downregulated. GO analysis of upregulated genes showed enrichment in processes such as extracellular matrix organization, cell proliferation, and adhesion. Downregulated genes were associated with oxidative phosphorylation and adenosine triphosphate (ATP) biosynthesis. Notably, 59 out of 88 upregulated genes are known targets of downregulated miRNAs. Network analysis identified interactions between downregulated miRNAs and upregulated genes involved in key biological processes relevant to POAG pathogenesis. CONCLUSIONS: This study provides new insights into the potential role of NPCE-derived EVs and their miRNA cargo in POAG, suggesting novel mechanisms for disease progression and potential therapeutic targets for further investigation.