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Abstract #109745 Published in IGR 24-1

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

Liao J; Peng B; Huang G; Diao C; Qin Y; Hong Y; Lin J; Lin Y; Jiang L; Tang N; Tang F; Liang J; Zhang J; Yan Y; Chen Q; Zhou Z; Shen C; Huang W; Huang K; Lan Q; Cui L; Zhong H; Xu F; Li M; Wei Y; Lu P; Zhang M
Biomedicine & pharmacotherapy = Biomédecine & pharmacothérapie 2023; 165: 115052


Reactive oxygen species (ROS) overproduction plays an essential role in the etiology of ischemic/hypoxic retinopathy 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 elucidated. Therefore, the current study aims to investigate the NOX4 inhibitor GLX351322 that targets NOX4 inhibition 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 inhibitor 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-1α, NF-κB, 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.

Institute of Ophthalmic Diseases, Guangxi Academy of Medical Sciences & Department of Ophthalmology, the People's Hospital of Guangxi Zhuang Autonomous Region & Guangxi Key Laboratory of Eye Health & Guangxi Health Commission Key Laboratory of Ophthalmology and Related Systemic Diseases Artificial Intelligence Screening Technology, Nanning 530000, Guangxi, China.

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15 Miscellaneous



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