# Unveiling Systemic Biomarkers and Metabolic Mechanisms in Glaucoma Progression from Multi-Omics Insights

## TL;DR

This study identifies blood and urine biomarkers linked to glaucoma progression and reveals metabolic mechanisms involving calcium and glucose.

## Contribution

The study introduces a multi-omics approach to uncover systemic biomarkers and metabolic pathways associated with glaucoma.

## Key findings

- Glaucoma is associated with elevated calcium levels in blood and urine, mediated by calcium channels and intracellular storage.
- High glucose levels increase glaucoma risk through mechanisms like increased intraocular pressure and oxidative stress.
- Elevated calcium and glucose levels were validated in glaucoma patients and shown to affect retinal cell viability.

## Abstract

Early diagnosis of glaucoma remains challenging due to its asymptomatic onset and multifactorial pathological mechanisms. Growing evidence indicates that metabolic disorders and systemic molecular alterations play significant roles in glaucoma pathogenesis. However, reliable biomarkers and corresponding specific mechanisms remain unclear. In this study, we employed a multi-omics approach that encompassed metabolomics, transcriptomics, and Mendelian randomization to investigate the association between glaucoma and 35 types of blood and urine biomarkers. Metabolic pathway analysis was conducted using pathway enrichment analysis of differentially expressed genes based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Our study indicated that glaucoma contributed to elevated calcium concentration (OR = 1.044, 95% CI: 1.002–1.088, p = 0.039) in blood and urine, mediated by cell membrane calcium channels and calcium release from intracellular storage. Conversely, glucose was found to contribute to high glaucoma risk (OR = 1.324, 95% CI: 1.143–1.533, p = 0.0002), mediated by increased aqueous humor production, elevated intraocular pressure, endoplasmic reticulum stress, and oxidative stress. Validation experiments showed that calcium levels in blood, urine, and retina were elevated in the glaucoma group, and elevated glucose levels significantly reduced the 661W cell viability and induced apoptosis. This study offers new insights into the specific mechanisms linking blood and urine biomarkers to glaucoma, contributing to its prevention and screening.