Vision Changes after Spaceflight Are Related to Alterations in Folate- and Vitamin B-12-Dependent One-Carbon Metabolism,

Abstract

Approximately 20% (7 of 38) of astronauts on International Space Station (ISS) missions have developed measurable ophthalmic changes after flight. This study was conducted to determine if the folate- and vitamin B-12-dependent 1-carbon metabolic pathway is altered in these individuals. Since 2006, we have conducted experiments on the ISS to evaluate nutritional status and related biochemical indices of astronauts before, during, and after flight. Data were modeled to evaluate differences between individuals with ophthalmic changes (n = 5) and those without them (n = 15), all of whom were on ISS missions of 48-215 d. We also determined whether mean preflight serum concentrations of the 1-carbon metabolites and changes in measured cycloplegic refraction after flight were associated. Serum homocysteine (Hcy), cystathionine, 2-methylcitric acid (2MCA), and methylmalonic acid concentrations were 25-45% higher (P < 0.001) in astronauts with ophthalmic changes than in those without them. These differences existed before, during, and after flight. Preflight serum concentrations of Hcy and cystathionine, and mean in-flight serum folate, were correlated with change (postflight relative to preflight) values in refraction (P < 0.05), and preflight serum concentrations of 2MCA tended to be associated (P = 0.06) with ophthalmic changes. The biochemical differences observed in crewmembers with vision issues strongly suggest that their folate- and vitamin B-12-dependent 1-carbon transfer metabolism was affected before and during flight. The consistent differences in markers of 1-carbon metabolism between those who did and those who did not develop changes in vision suggest that polymorphisms in enzymes of this pathway may interact with microgravity to cause these pathophysiologic changes.

Analysis of MTHFR, CBS, Glutathione, Taurine, and Hydrogen Sulfide Levels in Retinas of Hyperhomocysteinemic Mice

“…For examples, higher serum Hcy levels and altered one-carbon metabolism have been reported in a subset of astronauts on the International Space Station who developed ophthalmic changes including altered NFL thickness, optic disc edema, globe flattening, choroidal folds, hyperopic shifts, and cotton wool spots. 44 There was no evidence of glaucoma or central retinal vein occlusion in the astronauts.…”

Space Flight Ophthalmic Changes, Diet, and Vitamin Metabolism

“…[27][28][29][30] 14 Vitamin B 12 or folate deficiencies, even those that are detected by screening of asymptomatic populations, can cause optic neuropathies such as optic disc swelling and vision impairment.…”

“…• Cataract incidence is increased by space flight, secondary to radiation and oxygen exposure, Table 1 in Zwart et al (2012). • Cataract incidence is increased by space flight, secondary to radiation and oxygen exposure, Table 1 in Zwart et al (2012).…”

Folate Transport in Retina and Consequences on Retinal Structure and Function of Hyperhomocysteinemia

“…[75][76][77] Recently, very important clinical findings have emerged from studies of visual function during and after long-term spaceflight. 79 The biochemical differences observed in crew members with visual deficits strongly suggest that folate-and vitamin B 12 -dependent one-carbon transfer metabolism was affected before and during flight. 78 The cause of the ophthalmic changes is not known, but the initial report suggested that perhaps microgravity-induced cephalad fluid shifts or localized intraorbital changes were involved.…”