# Pyrroloquinoline Quinone (PQQ) Attenuates Hydrogen Peroxide-Induced Injury Through the Enhancement of Mitochondrial Function in Human Trabecular Meshwork Cells

## TL;DR

PQQ helps protect human eye cells from oxidative stress by improving mitochondrial function, which could lead to new treatments for glaucoma.

## Contribution

This study is the first to show PQQ's protective effects on human trabecular meshwork cells under oxidative stress.

## Key findings

- PQQ improves mitochondrial respiration and ATP production in HTM cells.
- PQQ reduces H2O2-induced damage and preserves mitochondrial function.
- PQQ partially restores mitochondrial structure and reduces cell death.

## Abstract

Mitochondrial metabolism in the trabecular meshwork (TM) plays a critical role in maintaining intraocular pressure homeostasis by supporting the energy-demanding processes involved in aqueous humour outflow. In primary open-angle glaucoma, oxidative stress impairs mitochondrial function, leading to TM dysfunction. Therefore, understanding and targeting mitochondrial health in TM cells could offer a novel therapeutic strategy. Pyrroloquinoline quinone (PQQ) is a redox cofactor with antioxidant and mitochondrial-enhancing properties. However, its effects on human TM (HTM) cells remain largely unexplored. This study examined PQQ cytoprotective effects against H2O2-induced oxidative stress in HTM cells. Seahorse analyses revealed that PQQ alone improves mitochondrial respiration and ATP production. Moreover, PQQ mitigates H2O2-induced cellular damage and preserves mitochondrial function by normalising proton leak and increasing ATP levels. Furthermore, TEM and confocal microscopy showed that PQQ can partially alleviate structural damage, restoring mitochondrial network morphology, thereby leading to reduced cell death. Although these protective effects seem not to be mediated by changes in mitochondrial content or activation of the SIRT1/PGC1-α pathway, they may involve modulation of SIRT3, a key factor of mitochondrial metabolism and homeostasis. Overall, these results suggest that PQQ may represent a promising candidate for restoring mitochondrial function and reversing oxidative damage in HTM cells.