# Peripheral Blood Mononuclear Cell Oxygen Consumption and Systemic Bioenergetics in Glaucoma Management

## TL;DR

This paper explores how mitochondrial dysfunction and metabolic issues in blood cells may contribute to glaucoma, suggesting new ways to assess and treat the disease.

## Contribution

The paper introduces systemic metabolic profiling as a novel tool for glaucoma risk assessment and treatment.

## Key findings

- Glaucoma patients show lower PBMC oxygen consumption rates and reduced NAD+ levels compared to healthy individuals.
- Systemic respiratory performance correlates with faster visual field loss and retinal thinning, independent of IOP.
- Defective mitophagy and Complex I defects suggest new therapeutic targets like nicotinamide and coenzyme Q10.

## Abstract

Glaucoma is a multifaceted optic neuropathy, characterized by the progressive loss of retinal ganglion cells. This damage frequently continues even after intraocular pressure (IOP) has been effectively lowered. This resistance to conventional IOP-lowering therapy underscores the critical role of interacting IOP-independent mechanisms; specifically metabolic failure and systemic mitochondrial dysfunction have emerged as key parallel drivers. This review analyzes the paradigm shift from a pressure-centric model to a bioenergetic one, focusing on mitochondrial function, peripheral blood mononuclear cell (PBMC) biomarkers, and oxygen consumption dynamics. We synthesize evidence demonstrating that glaucoma patients exhibit a metabolic vulnerability, characterized by lower PBMC oxygen consumption rates and depleted systemic nicotinamide adenine dinucleotide levels relative to healthy individuals. Furthermore, compromised systemic respiratory performance correlates with more rapid worsening of visual fields and structural thinning, independent of IOP status. Moreover, we delineate the role of Complex I defects, SARM1-mediated axonal degeneration, and proteomic alterations, which indicate defective mitophagy. These findings establish systemic metabolic profiling as a valuable supplementary tool for assessing patient risk and support the clinical translation of neuroprotective therapies targeting mitochondrial bioenergetics, specifically nicotinamide, pyruvate, coenzyme Q10, and metformin.