Glaucoma, a neurodegenerative disorder that leads to irreversible blindness, remains a challenge because of its complex nature. MicroRNAs (miRNAs) are crucial regulators of gene expression and are associated with glaucoma and other diseases. We aimed to review and discuss the advantages and disadvantages of miRNA-focused molecular studies in glaucoma through discussing their potential as biomarkers for early detection and diagnosis; offering insights into molecular pathways and mechanisms; and discussing their potential utility with respect to personalized medicine, their therapeutic potential, and non-invasive monitoring. Limitations, such as variability, small sample sizes, sample specificity, and limited accessibility to ocular tissues, are also addressed, underscoring the need for robust protocols and collaboration. Reproducibility and validation are crucial to establish the credibility of miRNA research findings, and the integration of bioinformatics tools for miRNA database creation is a valuable component of a comprehensive approach to investigate miRNA aberrations in patients with glaucoma. Overall, miRNA research in glaucoma has provided significant insights into the molecular mechanisms of the disease, offering potential biomarkers, diagnostic tools, and therapeutic targets. However, addressing challenges such as variability and limited tissue accessibility is essential, and further investigations and validation will contribute to a deeper understanding of the functional significance of miRNAs in glaucoma.

Glaucoma is a progressive neurodegenerative disease of the optic nerve and one of the leading causes of irreversible blindness worldwide. Small RNAs (including miRNAs) play an important role in the pathogenesis of the disease. Despite extensive research, the exact mechanisms underlying glaucoma remain incompletely understood and current diagnostic tools primarily detect the disease at later stages, when substantial neuronal loss has already occurred. This study aimed to comprehensively analyze small RNA expression in the aqueous humor of patients with glaucomatous disease and identify specific RNA biomarkers associated with disease progression. This prospective, single-center, cross-sectional study involved 51 individuals: 31 adult patients with primary open-angle glaucoma (POAG) and 20 patients with cataracts qualified for elective surgery. A gradient-boosting decision tree classifier was implemented to classify POAG from cataracts. The model performance was rigorously assessed during cross-validation using a suite of metrics, including receiver operating characteristic (ROC) curves, area under the ROC curve, accuracy, recall, sensitivity, F1 score, specificity, precision, and negative predictive value. Expression of hsa-miR-21-5p was significantly higher in POAG than that in cataracts, indicating its potential as both a biomarker and therapeutic target. Moreover, miR-210-3p expression was associated with apoptosis occurrence in trabecular meshwork cells treated with TGF-β1. Our study highlights the diagnostic potential of small-RNAs for distinguishing POAG from cataracts by integrating molecular profiling with advanced bioinformatics approaches. These findings provide new avenues for early diagnosis, personalized medicine, and improved clinical management.