GPX4 Promotes Optic Nerve Regeneration and RGC Neuroprotection

  1. Ming Yang
  2. Fuyun Bian
  3. Xue Feng
  4. Liang Li
  5. Haoliang Huang
  6. Liang Liu
  7. Roopa Dalal
  8. Hang Yang
  9. Pranav Varma Suraparaju
  10. Frank Cao
  11. Petrina Ong
  12. Alexandria Luo
  13. Dong Liu
  14. Yang Hu
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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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  1. Version published to 10.1101/2025.06.03.657677v1 on bioRxiv