| Title: | Dysfunctional one-carbon metabolism identifies vitamins B6, B9, B12, and choline as neuroprotective in glaucoma |
| Journal: | Cell Reports Medicine |
| Published: | 8 May 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40345183/ |
| DOI: | https://doi.org/10.1016/j.xcrm.2025.102127 |
| URL: | https://www.cell.com/action/showPdf?pii=S2666379125002009 |
Publication 15400
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Abstract
Glaucoma, characterized by the loss of retinal ganglion cells (RGCs), is a leading cause of blindness for which there are no neuroprotective therapies. To explore observations of elevated homocysteine in glaucoma, we elevate vitreous homocysteine, which increases RGC death by 6% following ocular hypertension. Genetic association with higher homocysteine does not affect glaucoma-associated outcomes from the UK Biobank and serum homocysteine levels have no effect on glaucomatous visual field progression. This supports a hypothesis in which elevated homocysteine is a pathogenic, rather than causative, feature of glaucoma. Further exploration of homocysteine metabolism in glaucoma animal models demonstrates early and sustained dysregulation of genes involved in one-carbon metabolism and the interaction of essential cofactors and precursors (B6, B9, B12, and choline) in whole retina and optic nerve head and RGCs. Supplementing these provides neuroprotection in an acute model and prevents neurodegeneration and protects visual function in a chronic model of glaucoma.</p>
14 Keywords
- Animals
- Carbon
- Choline
- Disease Models, Animal
- Female
- Glaucoma
- Homocysteine
- Humans
- Male
- Neuroprotection
- Neuroprotective Agents
- Retinal Ganglion Cells
- Vitamin B 12
- Vitamin B 6
20 Authors
- James R. Tribble
- Vickie H.Y. Wong
- Kelsey V. Stuart
- Glyn Chidlow
- Alan Nicol
- Anne Rombaut
- Alessandro Rabiolo
- Anh Hoang
- Pei Ying Lee
- Carola Rutigliani
- Tim J. Enz
- Alessio Canovai
- Emma Lardner
- Gustav Stålhammar
- Christine T.O. Nguyen
- David F. Garway-Heath
- Robert J. Casson
- Anthony P. Khawaja
- Bang V. Bui
- Pete A. Williams
1 Application
| Application ID | Title |
|---|---|
| 36741 | Discovering the biological mechanisms underlying glaucoma and neurodegeneration by analysis of genetic and environmental determinants and associations with other systemic traits in the UK Biobank |
Enabling scientific discoveries that improve human health