Protective effects of methylcobalamin, a vitamin B12 analog, against glutamate-induced neurotoxicity in retinal cell culture

Invest Ophthalmol Vis Sci. 1997 Apr;38(5):848-54.


Purpose: To examine the effects of methylcobalamin on glutamate-induced neurotoxicity in the cultured retinal neurons.

Methods: Primary cultures obtained from the fetal rat retina (gestation days 16 to 19) were used for the experiment. The neurotoxicity was assessed quantitatively using the trypan blue exclusion method.

Results: Glutamate neurotoxicity was prevented by chronic exposure to methylcobalamin and S-adenosylmethionine (SAM), which is formed in the metabolic pathway of methylcobalamin. Chronic exposure to methylcobalamin and SAM also inhibited the neurotoxicity induced by sodium nitroprusside that release nitric oxide. By contrast, acute exposure to methylcobalamin did not protect retinal neurons against glutamate neurotoxicity.

Conclusions: Chronic administration of methylcobalamin protects cultured retinal neurons against N-methyl-D-aspartate-receptor-mediated glutamate neurotoxicity, probably by altering the membrane properties through SAM-mediated methylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Cell Death / drug effects
  • Cell Survival / drug effects*
  • Cells, Cultured
  • Coloring Agents
  • Glutamic Acid / toxicity*
  • Neurons / cytology
  • Neurons / drug effects*
  • Nitroprusside / toxicity
  • Rats
  • Retina / cytology
  • Retina / drug effects*
  • Retina / embryology
  • S-Adenosylmethionine / pharmacology
  • Sulfhydryl Reagents / toxicity
  • Trypan Blue
  • Vitamin B 12 / analogs & derivatives*
  • Vitamin B 12 / pharmacology


  • Coloring Agents
  • Sulfhydryl Reagents
  • Nitroprusside
  • Glutamic Acid
  • S-Adenosylmethionine
  • mecobalamin
  • Trypan Blue
  • Vitamin B 12
  • Calcium