B vitamins and choline prevent retinal degeneration in glaucoma models
Karolinska Institutet researchers demonstrated that metabolic cofactors protect retinal ganglion cells and preserve visual function in animal models of glaucoma.
Glaucoma, a condition characterized by the loss of retinal ganglion cells (RGCs), remains a primary cause of blindness lacking neuroprotective therapies. In a study published in Cell Reports Medicine, researchers from Karolinska Institutet investigated the role of homocysteine metabolism and dietary cofactors in retinal cell survival sciencedirect.com
Cell Reports Medicinesciencedirect.comOpen source ↗. Elevating vitreous homocysteine in models increased RGC death by 6% following ocular hypertension, though analysis of UK Biobank cohorts revealed that genetic predisposition to elevated homocysteine had no effect on glaucoma-associated outcomes or visual field loss progression. These findings led researchers to conclude that elevated homocysteine functions as a pathogenic marker rather than a direct causative driver of the pathology.
Dysregulation of one-carbon metabolism
Further exploration in animal models revealed early and sustained dysregulation of genes governing one-carbon metabolism in the whole retina, optic nerve head, and isolated RGCs. The disruption directly altered the interaction of vital precursors and cofactors, specifically vitamins B6, B9, B12, and choline. Because human population data showed no direct link between dietary B-vitamin intake and visual outcomes, the team focused on supplementing these metabolic components directly to stabilize the disrupted cellular pathways in vivo.
Neuroprotection in acute and chronic models
Supplementing animals with a combination of vitamins B6, B9, B12, and choline delivered neuroprotection in an acute model of ocular hypertension. In a chronic glaucoma model, the cofactors prevented neurodegeneration and preserved visual function over time. The neuroprotective effect occurred independently of changes in intraocular pressure, presenting a distinct pathway to target cellular metabolism directly. Clinical testing at S:t Eriks Eye Hospital has commenced to determine human safety, therapeutic dosages, and clinical efficacy in patients.
