Cobalamin-Associated Superoxide Scavenging in Neuronal Cells Is a Potential Mechanism for Vitamin B12-Deprivation Optic Neuropathy.

PubMed ID: 29037851

Author(s): Chan W, Almasieh M, Catrinescu MM, Levin LA. Cobalamin-associated superoxide scavenging in neuronal cells Is a potential mechanism for vitamin B(12)-deprivation optic neuropathy. Am J Pathol. 2018 Jan;188(1):160-172. doi: 10.1016/j.ajpath.2017.08.032. Epub 2017 Oct 14. PMID 29037851

Journal: The American Journal Of Pathology, Volume 188, Issue 1, Jan 2018

Chronic deficiency of vitamin B12 is the only nutritional deficiency definitively proved to cause optic neuropathy and loss of vision. The mechanism by which this occurs is unknown. Optic neuropathies are associated with death of retinal ganglion cells (RGCs), neurons that project their axons along the optic nerve to the brain. Injury to RGC axons causes a burst of intracellular superoxide, which then signals RGC apoptosis. Vitamin B12 (cobalamin) was recently shown to be a superoxide scavenger, with a rate constant similar to superoxide dismutase. Given that vitamin B12 deficiency causes an optic neuropathy through unknown mechanisms and that it is a potent superoxide scavenger, we tested whether cobalamin, a vitamin B12 vitamer, would be neuroprotective in vitro and in vivo. We found that cobalamin scavenged superoxide in neuronal cells in vitro treated with the reduction-oxidation cycling agent menadione. In vivo confocal scanning laser ophthalmoscopy demonstrated that optic nerve transection in Long-Evans rats increased superoxide levels in RGCs. The RGC superoxide burst was significantly reduced by intravitreal cobalamin and resulted in increased RGC survival. These data demonstrate that cobalamin may function as an endogenous neuroprotectant for RGCs through a superoxide-associated mechanism.