Vitamins B6, B9 and B12 were found to be neuroprotective against retinal ganglion cell death
Investigators from the Department of Clinical Neuroscience and Division of Eye and Vision at St. Erik Eye Hospital in Stockholm, Sweden, reported their results in Cell Reports Medicine. Image credit: ©itsflowingtothesoul – stock.adobe.com
Swedish researchers, led by senior author James R. Tribble, BSc, PhD, reported that oral B6, B9, B12 and choline were neuroprotective against glaucoma in two animal models. The investigators are from the Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden. They reported their results in Cell Reports Medicine.
There currently are no neuroprotective therapies available to treat glaucoma, and discovery is complicated by the disease complexity, the investigators commented.
“Recent work has identified metabolic dysfunction in the retina and optic nerve occurring prior to detectable neurodegeneration of retinal ganglion cells (RGCs) in glaucoma (via transcriptomic and metabolomic analyses), presenting the potential for neuroprotection prior to the initiation of neurodegenerative cascades. Loss of mitochondrial function and transport in RGCs,2,3 reduced energy capacity,4 loss of the ability to maintain nicotinamide adenine dinucleotide5,6 and the depletion of alternative energy sources7,8 have all been identified early in glaucoma in human patients and animal models,” they explained.
The authors cited studies in which elevated levels of homocysteine were associated with major diseases such as cardiovascular disease, diabetes and Alzheimer disease, although this is typically in the form of hyperhomocysteinemia, where homocysteine is elevated in the blood.9 In addition, small human studies have suggested that homocysteine may be elevated in the blood and aqueous humor of certain glaucomas.10 Mouse models of hyperhomocysteinemia present significant retinal degenerative phenotypes, including vascular compromise and RGC degeneration.11-13 Supporting this, intravitreal injection of homocysteine in high concentrations can induce RGC death.14,15
Based on those studies, Dr Tribble and colleagues hypothesised that elevated homocysteine directly compounds RGC death in glaucoma and is related to dysfunction in one-carbon metabolism.
To determine this, they used mouse and rat models of ocular hypertension and retrospectively evaluated human epidemiologic data to investigate the effect of homocysteine and one-carbon metabolism, a pathway that transfers one-carbon units to molecules, and their impact on neurodegeneration.
“Our study demonstrated that elevated homocysteine worsens glaucoma outcome in animal models but this effect is mild. In humans, elevation of serum homocysteine has no detectable effect on glaucoma-related outcomes or disease progression. Early elevation of homocysteine in the retina is a marker of dysfunctional one-carbon metabolism, which we identify as an early and sustained feature of glaucoma. This is associated with dysfunctional regulation of genes and proteins that interact with key one-carbon metabolism cofactors and precursors: vitamin B6, B9, B12 and choline,” they reported.
Importantly, this supplementation of vitamin B6, B9, B12 and choline provided neuroprotection against the death of RGCs in acute and mild and chronic animal models of glaucoma, including protection of visual function. This was independent of the intraocular pressure.
Dr Tribble and colleagues believe these findings ultimately can be useful in treatment of humans with glaucoma.
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