Comprehensive small non-coding RNA profiling reveals novel diagnostic biomarkers for primary open-angle glaucoma

Primary open-angle glaucoma (POAG) is the most prevalent type of glaucoma, and early-stage optic neuropathy may cause visual field defects. As these early defects have minimal effects on vision, they are often overlooked, resulting in the loss of optimal treatment timing. Urgent identification of novel early diagnostic biomarkers is needed. In this study, blood samples from 30 POAG patients and 30 healthy controls were analyzed for Small Non-Coding RNAs (sncRNAs) transcriptomics and validated. We performed PANDORA-seq to profile quantitative sncRNAs signature, and a total of 169 differentially expressed sncRNAs were identified, including 147 PIWI-interacting RNAs, 10 microRNAs, and 12 transfer RNA-derived small RNAs. Functional enrichment analysis of sncRNAs target genes revealed significant involvement in key pathological processes, including apoptosis, inflammation, and intraocular pressure homeostasis. Regulatory network analysis demonstrated substantial functional overlap among different sncRNAs groups, suggesting potential cooperative roles in POAG pathogenesis. The expressions of 6 candidate sncRNAs were validated by quantitative real-time polymerase chain reaction, confirming the downregulation of tsRNA-5009b-ValCAC (p < 0.05), piR-hsa-767,596 (p < 0.05), piR-hsa-731,834 (p < 0.01) and hsa-miR-451a (p < 0.05) in POAG patients. Besides, receiver operating characteristic (ROC) curve analysis demonstrated that individual sncRNAs exhibited moderate diagnostic performance, with hsa-miR-451a showing good performance (AUC = 0.83).Our study provides novel insights into the role of sncRNAs in POAG and highlights their potential as diagnostic biomarkers for early disease detection and monitoring.