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

Abstract

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. 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. 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. 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. 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. 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.