Summary: Glaucoma damages the optic nerve and is usually managed by reducing eye pressure, though treatment effects vary. Researchers have long suspected a link with homocysteine, but new findings reveal it is a bystander, not a driver of the disease.
Instead, metabolic disruptions affecting the retina’s vitamin use appear key, prompting scientists to test vitamin B6, B9, B12, and choline supplements in animal models. Remarkably, this vitamin mix halted or slowed nerve damage without reducing eye pressure, and a clinical trial is now underway to test its potential in humans.
Key facts:
- Homocysteine Role Debunked: High homocysteine does not drive glaucoma but reflects metabolic changes.
- Vitamin Therapy Promising: B vitamin and choline supplements halted or slowed optic nerve damage in rodents.
- Human Trials Begun: A clinical trial is now recruiting patients to test this approach in slowing glaucoma progression.
Source: Karolinska Institute
In glaucoma, the optic nerve is gradually damaged, leading to vision loss and, in the worst cases, blindness.
High pressure in the eye drives the disease, and eye drops, laser treatment or surgery are therefore used to lower the pressure in the eye and thus slow down the disease. Unfortunately, however, the effect varies.
Glaucoma researchers have long theorised that the substance homocysteine is somehow relevant to understanding the disease.
Now, researchers at Karolinska Institutet have investigated the role of homocysteine in several ways. In the current study, the researchers discovered that when rats with glaucoma were given elevated levels of homocysteine, their disease did not worsen.
The researchers also found that high levels of homocysteine in the blood of people with glaucoma did not correlate with how quickly the disease progressed, and that glaucoma was not more common in people with a genetic susceptibility to forming high levels of homocysteine. Based on these findings, the researchers concluded that homocysteine does not drive the disease but is a consequence of it.
Since homocysteine is a natural part of the body’s metabolism, the researchers wanted to investigate metabolic pathways involving homocysteine in both rodents and humans with glaucoma.
They then saw several abnormalities, the most important of which were metabolic changes linked to the retina’s ability to use certain vitamins. This change meant that metabolism was slowed down locally in the retina – and this played a role in the development of the disease.
‘Our conclusion is that homocysteine is a bystander in the disease process, not a player. Altered homocysteine levels may reveal that the retina has lost its ability to use certain vitamins that are necessary to maintain healthy metabolism.
“That’s why we wanted to investigate whether supplements of these vitamins could protect the retina,’ says co-lead on the paper James Tribble, researcher and assistant professor at the Department of Clinical Neuroscience at Karolinska Institutet.
In experiments on mice and rats with glaucoma, the researchers gave supplements of the B vitamins B6, B9 and B12, as well as choline. This had a positive effect.
In mice that had a slower developing glaucoma, the damage to the optic nerve was completely halted. In rats, which had a more aggressive form of the disease with faster progression, the disease was slowed down.
In these experiments, eye pressure was left untreated, which the researchers highlight as particularly interesting – it suggests that the vitamin mix affects the disease in a different way than lowering eye pressure does.
‘The results are so promising that we have started a clinical trial, with patients already being recruited at S:t Eriks Eye Hospital in Stockholm,’ says James Tribble.
Both patients with primary open-angle glaucoma (slower progression) and pseudoexfoliation glaucoma (faster progression) are included.
Read more about the clinical trial here. (https://nyheter.ki.se/forskningspersoner-sokes/har-du-glaukom-gron-starr-och-vill-du-vara-med-i-en-studieom study).
Funding: The study is funded by the Swedish Research Council, the Swedish Eye Health Fund, the Jeansson Foundations, the Crown Princess Margareta Foundation for the Visually Impaired, the Åke Wiberg Foundation and the Petrus & Augusta Hedlund Foundation, among others.
About this visual neuroscience and glaucoma research news
Author: Press Office
Source: Karolinska Institute
Contact: Press Office – Karolinska Institute
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Dysfunctional one-carbon metabolism identifies vitamins B6, B9, B12, and choline as neuroprotective in glaucoma” by James Tribble et al. Cell Reports Medicine
Abstract
Dysfunctional one-carbon metabolism identifies vitamins B6, B9, B12, and choline as neuroprotective in glaucoma
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.
