(P11-057-23) Genetics of One-Carbon Metabolism Are Associated With Optic Disc Edema in a Ground-Based Model of Spaceflight

Objectives: Optic disc edema, one of the pathologic findings of spaceflight associated neuro-ocular syndrome (SANS) presents in some astronauts on the International Space Station. Previously, 30-d strict head down tilt bed rest (HDTBR) in a 0.5% CO₂ environment was used to simulate effects of spaceflight. Subjects with 3–4 risk alleles (G and C alleles from the methionine synthase reductase [MTRR] A66G and serine hydroxymethyltransferase [SHMT1] C1420T) had a greater change in total retinal thickness (ΔTRT) than subjects with 1–2 risk alleles. One limitation is that all subjects were exposed to 0.5% CO₂, compared to typical 0.05%.

We sought to validate a SANS outcomes statistical model in a 60-d HDTBR study without elevated ambient CO₂.

Methods: Optical coherence tomography was used to measure peripapillary TRT and retinal nerve fiber layer thickness. 24 subjects participated in the study, 22 provided blood samples for genetic analysis. The study groups included 30 minutes daily intermittent or continuous artificial gravity (centrifugation at 1 Gz at the center of mass), which had no effect on ΔTRT, hence, all subjects’ data were combined.

Results: Subjects with 3–4 risk alleles had a greater ΔTRT during and after HDTBR than subjects with 0–2 risk alleles. After 30-d of bed rest, the ΔTRT was a lower (P < 0.05) when compared to a previous study where HDTBR subjects were maintained in a 0.5% CO₂ environment.

Conclusions: This study reaffirms an association between genetic variants of MTRR and SHMT1 and ocular pathologies during HDTBR. Whether the difference in response between these studies is related to an effect of CO₂ exposure on genetically predisposed optic disc edema or is an artifact of an unknown difference between the two studies is unknown. A study is underway to assess whether B vitamin supplements can override genetic influences on biochemistry and pathophysiology. These data provide a potential pathway for understanding susceptibility to SANS development in astronauts. Ultimately, understanding the mechanism(s) will provide a means to predict, prevent, and/or treat astronaut ophthalmologic pathologies. Furthermore, this work may have significant implications for terrestrial medicine.

Funding Sources: This study was funded by the NASA Human Research Program’s Human Health Countermeasures Element.