ArticleMolecular therapy : the journal of the American Society of Gene Therapy2026
GPX4 promotes optic nerve regeneration and retinal ganglion cell neuroprotection.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Cuproptosis and ferroptosis: signal pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Immunological drivers of oxidative stress in glaucoma: implications for antioxidant therapy.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026Review
- Anti-Apoptotic and Neurite-Protective Nanomedicine Augments Embryonic Stem Cells-Derived Retinal Ganglion Cell Transplantation in Glaucoma Recovery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Technological advances in axonal regeneration and structural plasticity: optogenetics, single-cell omics, and tissue clearing.Frontiers in cellular neuroscience · 2026Review
- Ferroptosis in retinal neurodegeneration: mechanistic vulnerability, therapeutic targeting, and translational barriers.Frontiers in medicine · 2026Review
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
Glaucoma is an optic neuropathy characterized as progressive degeneration of retinal ganglion cells (RGCs) and their axons in the optic nerve (ON). Recently, lipid peroxidation and ferroptosis have been linked to experimental glaucoma, suggesting a new therapeutic strategy. Here, we report that glutathione peroxidase 4 (GPX4), a key regulator of lipid peroxidation, is upregulated in surviving and regenerating RGCs in two mouse optic neuropathy models, traumatic ON crush and glaucoma. To explore the potential neuroprotective role of GPX4, we test adeno-associated virus-mediated RGC-specific overexpression of GPX4 in these models and found that GPX4 promotes significant ON regeneration, RGC survival, and visual functional preservation. Interestingly, lipid peroxidation inhibitor liproxstatin-1, but not ferroptosis inhibitor deferiprone, presents significant RGC neuroprotection and axon regeneration, indicating the detrimental role of lipid peroxidation but not ferroptosis in optic neuropathies, and the therapeutic potential of modulating lipid peroxidation through GPX4.
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Registered trials
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