Dysfunctional one-carbon metabolism identifies vitamins B<sub>6</sub>, B<sub>9</sub>, B<sub>12</sub>, and choline as neuroprotective in glaucoma.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 40345183.
- Also identified by DOI 10.1016/j.xcrm.2025.102127 and PMC identifier 12147907.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 (B<sub>6</sub>, B<sub>9</sub>, B<sub>12</sub>, 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.
Medical subject headings
- Glaucoma
- Choline
- Neuroprotective Agents
- Vitamin B 6
- Vitamin B 12
- Carbon