Inhibition of NOX4 with GLX351322 alleviates acute ocular hypertension-induced retinal inflammation and injury by suppressing ROS mediated redox-sensitive factors activation

Reactive oxygen species (ROS) overproduction plays an essential role in the etiology of ischemic/hypoxic reti-nopathy caused by acute glaucoma. NADPH oxidase (NOX) 4 was discovered as one of the main sources of ROS in glaucoma. However, the role and potential mechanisms of NOX4 in acute glaucoma have not been fully eluci-dated. Therefore, the current study aims to investigate the NOX4 inhibitor GLX351322 that targets NOX4 in-hibition in acute ocular hypertension (AOH)-induced retinal ischemia/hypoxia injury in mice. Herein, NOX4 was highly expressed in AOH retinas, particularly the retinal ganglion cell layer (GCL). Importantly, the NOX4 in-hibitor GLX351322 reduced ROS overproduction, inhibited inflammatory factor release, suppressed glial cell activation and hyperplasia, inhibited leukocyte infiltration, reduced retinal cell senescence and apoptosis in damaged areas, reduced retinal degeneration and improved retinal function. This neuroprotective effect is at least partially associated with mediated redox-sensitive factor (HIF-1 & alpha;, NF-& kappa;B, and MAPKs) pathways by NOX4-derived ROS overproduction. These results suggest that inhibition of NOX4 with GLX351322 attenuated AOH-induced retinal inflammation, cellular senescence, and apoptosis by inhibiting the activation of the redox-sensitive factor pathway mediated by ROS overproduction, thereby protecting retinal structure and function. Targeted inhibition of NOX4 is expected to be a new idea in the treatment of acute glaucoma.

Automated summary

The study investigates the role of NOX4 inhibitor GLX351322 in acute ocular hypertension-induced retinal injury. The inhibitor reduced ROS overproduction, inhibited inflammatory factor release, and suppressed glial cell activation and hyperplasia. It also improved retinal degeneration and function by inhibiting the redox-sensitive factor pathway mediated by ROS overproduction.