B Vitamins, Homocysteine, and Vascular Dysregulation in Glaucoma

This audio article is from VisualFieldTest.com.

Read the full article here: https://visualfieldtest.com/en/b-vitamins-homocysteine-and-vascular-dysregulation-in-glaucoma

Test your visual field online: https://visualfieldtest.com

Excerpt:

IntroductionGlaucoma 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 (). 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 () (). 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 () (). 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 ().Homocysteine and GlaucomaResearch 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 genetically higher homocysteine did not predict worse glaucoma outcomes (). This hints that high Hcy may be a pathogenic feature – a consequence or exacerbating factor – rather than a primary cause of glaucoma. Nonetheless, these animal models also showed that supplementing deficiencies in one-carbon metabolism (the biochemical pathways using B vitamins) can protect the nerve. Namely, giving a cocktail of vitamin B6, folic acid (B9), vitamin B12, and choline to glaucoma-model rodents prevented retinal ganglion cell loss and preserved visual function (). In short, high homocysteine appears to stress the optic nerve (especially in the context of metabolic or genetic defects), and B-vitamin–related pathways can counteract that stress.B Vitamins and Homocysteine ReductionVitamins B6, B9 (folate), and B12 are essential co-factors in homocysteine metabolism—B9 and B12 help remethylate homocysteine back to methionine, and B6 helps convert homocysteine to cystathionine for breakdown. Giving these vitamins reliably lowers plasma homocysteine. Meta-analyses show that supplementing folic acid, B6 and B12 reduces homocysteine by roughly 25–30% over several years (). In one large review of trials (over 22,000 participants), B-vitamin therapy cut total homocysteine by about 26–28% but had no significant effect on cognitive test scores or global mental function (). In practical terms, lowering Hcy with B vitamins did not slow down cognit