GPX4 Promotes Optic Nerve Regeneration and RGC Neuroprotection

  • bioRxiv. 2025 Jun 6:2025.06.03.657677. doi: 10.1101/2025.06.03.657677.
Ming Yang  1 ,  Fuyun Bian  1 ,  Xue Feng  1 ,  Liang Li  1 ,  Haoliang Huang  1 ,  Liang Liu  1 ,  Roopa Dalal  1 ,  Hang Yang  1 ,  Pranav Varma Suraparaju  2 ,  Frank Cao  3 ,  Petrina Ong  4 ,  Alexandria Luo  5 ,  Dong Liu  1 ,  Yang Hu  1
Affiliations
  • 1. Spencer Center for Vision Research, Department of Ophthalmology, Byers Eye Institute at Stanford University School of Medicine, Palo Alto, CA 94304, USA.
  • 2. Dougherty Valley High School, San Ramon (12th grade), California, United States.
  • 3. San Mateo High School, San Mateo, California, United States.
  • 4. Webb Schools, Claremont, California, United States.
  • 5. Oaks Christian School, Westlake Village, California, United States.
PMID: 40501672 DOI: 10.1101/2025.06.03.657677
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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