folate

# Introduction **Glaucoma** is an age-related optic neuropathy in which retinal ganglion cells and their fibers in the optic nerve gradually die, often silently, leading to vision loss. While high intraocular pressure is a well-known risk factor, blood vessel health also matters – poor blood flow or **vascular dysregulation** in the optic nerve head can contribute to glaucoma progression. **Homocysteine** (Hcy) is an amino acid metabolite that normally circulates at low levels (5–15 µmol/L) in the blood. When homocysteine rises (called *hyperhomocysteinemia*), it can injure endothelial cells (the inner lining of blood vessels) and promote oxidative stress and inflammation in the microvasculature ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC9884709/#:~:text=for%20it%20to%20promote%20AS,dietary%20therapy%20and%20supplementation%20of)). This endothelial dysfunction is a recognized step toward atherosclerosis and cardiovascular disease, and it may plausibly stress the small blood vessels that nourish the optic nerve. In fact, studies have long noted that people with glaucoma – especially certain types – tend to have higher homocysteine and lower folate (vitamin B9) levels ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC1402326/#:~:text=The%20mean%20Hcy%20concentration%20in,0.05)) ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC1402326/#:~:text=Elevated%20levels%20of%20Hcy%20in,dysfunction%20among%20patients%20with%20PEXG)). For example, in pseudoexfoliation glaucoma (a form of open-angle glaucoma), one study found significantly elevated homocysteine and correspondingly low folate; the authors concluded that “elevated levels of Hcy in [these patients] may explain the role of endothelial dysfunction” in that disease ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC1402326/#:~:text=The%20mean%20Hcy%20concentration%20in,0.05)) ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC1402326/#:~:text=Elevated%20levels%20of%20Hcy%20in,dysfunction%20among%20patients%20with%20PEXG)). In short, elevated homocysteine is known to damage blood vessels through **oxidative stress, inflammation, and impaired nitric oxide signaling**, and this could translate into optic nerve microvascular stress in glaucoma ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC9884709/#:~:text=for%20it%20to%20promote%20AS,dietary%20therapy%20and%20supplementation%20of)). ## Homocysteine and Glaucoma Research suggests that homocysteine-related vascular damage is relevant to glaucoma. For example, animal models of glaucoma show retinal metabolic disturbances long before nerve cell loss. In one recent study, normal (rodent) eyes exposed to intraocular pressure elevation had higher retinal homocysteine, and experimentally raising Hcy in the eye caused a small increase (≈6%) in ganglion cell death. Importantly, however, large genetic studies in humans (UK Biobank) found that having gene

B Vitamins, Homocysteine, and Vascular Dysregulation in Glaucoma

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