Association of Genetics and B Vitamin Status with the Magnitude of Optic Disc Edema during 30-Day Strict Head-Down Tilt Bed Rest

Importance: Optic disc edema among astronauts after long-duration spaceflight is associated with 1-carbon pathway single-nucleotide polymorphisms and B vitamin status. A recent strict 6° head-down tilt bed rest (HDTBR) study documented development of optic disc edema and increased total retinal thickness in participants exposed to carbon dioxide, 0.5%, for 30 days, but genetic risk factors have not been explored in the cohort. Objective: To examine whether peripapillary retinal thickness measures obtained from optical coherence tomography images during HDTBR and carbon dioxide, 0.5%, exposure are associated with B vitamin status and single-nucleotide polymorphisms involved in folate-dependent and vitamin B₁₂-dependent 1-carbon metabolism pathways. Design, Setting, and Participants: This study was conducted with a cohort of healthy volunteers at the Institute of Aerospace Medicine at the German Aerospace Center in Cologne, Germany. Data collection occurred from October 2017 to November 2017. After a 14-day ambulatory phase without carbon dioxide, participants maintained strict HDTBR with carbon dioxide, 0.5%, for 30 days, followed by a 13-day ambulatory phase without carbon dioxide. Main Outcomes and Measures: Blood samples were collected before HDTBR to assess vitamin levels and single-nucleotide polymorphism status. Optical coherence tomographic images were collected before HDTBR; at days 1, 15, and 30 of the resting period; and 6 and 13 days after the period ended. Total retinal thickness was measured from a radial-24 B-scan centered over the optic disc, and global retinal nerve fiber layer thickness was measured from a circle scan. The changes in total retinal thickness and retinal nerve fiber layer thickness were evaluated against the number of risk alleles (defined as 5-methyltetrahydrofolate-homocysteine methyltransferase reductase [MTRR] 66 G and serine hydroxymethyltransferase 1 [SHMT1] 1420C alleles), along with folate, vitamin B₆ (pyridoxine), and vitamin B₁₂ (cobalamin) status. Results: Eleven heathy volunteers (6 men and 5 women) had a mean (SD) age of 33.4 (8.0) years and a mean (SD) body mass index of 23.4 (2.2). After statistical adjustment for B vitamin status, total retinal thickness at the end of HDTBR in participants with 3 or 4 risk alleles was 40 um (SE, 19 μm) greater than in participants with 0 to 2 risk alleles. In addition, the baseline retinal nerve fiber layer thickness was 14 um (SE, 2 μm) greater in those with 3 or 4 risk alleles compared with those with 0 to 2 risk alleles. Conclusions and Relevance: The magnitude of optic disc edema in individuals experiencing HDTBR and exposed to a chronic headward fluid shift in a mild hypercapnic environment was higher in participants with more MTRR 66 G and SHMT1 1420C alleles, even when this finding was statistically adjusted for B vitamin status. These findings may help explain the variability in magnitude of optic disc edema observed during bed rest and spaceflight and thereby improve efforts to counteract this phenomenon.