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bioRxivNeurosciencePreprint

GPX4 Promotes Optic Nerve Regeneration and RGC Neuroprotection

Ming YangiD, Fuyun Bian, Xue FengiD, Liang LiiD, Haoliang HuangiD, Liang LiuiD, Roopa DalaliD, Hang YangiD, Pranav Varma SuraparajuiD, Frank Cao, Petrina Ong, Alexandria Luo, Dong LiuiD, Yang HuiD

PDFDOI

Abstract

Preventing retinal ganglion cells (RGCs)s soma and axon degeneration and promoting optic nerve (ON) regeneration holds great promise for effective glaucoma treatment. To explore potential neural repair strategies, we focused on glutathione peroxidase 4 (GPX4), a key regulator of lipid peroxidation. GPX4 is upregulated in surviving RGCs after acute ON crush or chronic ocular hypertension insult, and also in regenerating RGCs. AAV-mediated RGC-specific overexpression of GPX4 promotes significant ON regeneration and RGC survival, along with visual functional preservation, demonstrating the detrimental role of lipid peroxidation in glaucoma and the therapeutic potential of modulating lipid peroxidation through GPX4 in optic neuropathies.

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Ming Yang, Jie Pan, Shweta Modgil+10 more·bioRxiv·Aug 29, 2026