Transcriptomic analysis of plasma-derived small extracellular vesicles reveals the pathological characteristics of normal tension glaucoma

Aim: Normal tension glaucoma (NTG) is a common optic neuropathy that can be challenging to diagnose due to the intraocular pressure remaining within the normal range. Early diagnosis and intervention are crucial for the effective lifelong management of patients. Methods: This study recruited a total of 225 participants. Small extracellular vesicles (sEVs) RNA from circulating plasma was analyzed via transcriptomic sequencing, and its expression levels were verified by quantitative realtime polymerase chain reaction (qRT-PCR). Logistic regression, linear regression, and receiver operating characteristic (ROC) curve analyses were performed to examine the association of biomarkers with clinicopathological characteristics. Results: Analysis of sEVs mRNAs in NTG patients revealed mitochondrial dysfunction and enrichment of central nervous system degenerative pathways, reflecting the pathological features of NTG. Compared with those in the controls, the expression levels of sEVs let-7b-5p in the plasma of NTG patients were significantly lower, with an area under the curve (AUC) of 0.870 (95%CI: 0.797-0.943) (P P < 0.0001), and the AUC combined with age was 0.923 (95%CI: 0.851-0.996) (P P < 0.0001). In addition, we found that let-7b-5p levels were significantly correlated with the severity and visual field defects of NTG patients and had good specificity compared with other ophthalmic diseases. Conclusion: The sEVs RNA signatures in circulating plasma from NTG revealed mitochondrial dysfunction and that sEVs let-7b-5p can be a useful noninvasive biomarker for NTG.