MTRR 66 and SHMT1 1420 Variants Are Associated with Optic Disc Edema During 30-d Strict Head-down Tilt Bed Rest and CO2 Exposure (P24-036-19)

Abstract

Abstract Objectives Some astronauts returning from missions to the International Space Station (ISS) have developed ophthalmic structural changes, including optic disc edema. Incidence of optic disc edema among astronauts has been linked to one-carbon pathway genetic variants and B-vitamin status. A recent 30-d 6-degree head-down tilt bed rest study in which all subjects were exposed to 0.5% CO2 documented the occurrence of optic disc edema in 5 of 11 subjects. The objective of this study was to determine the effect of one-carbon pathway genetics and B-vitamin status on the incidence of optic disc edema in the bed rest subjects. Methods The study was conducted at the : envihab facility at the German Aerospace Center in Cologne, Germany. Subjects (6 M/5F) were healthy volunteers, 33 ± 8 y (mean ± SD), having a mean BMI of 23.4 ± 2.2 kg/m2. After a 14-d ambulatory phase in a standard environment (i.e., not hypercapnic), a blood sample was collected to assess vitamin status and single nucleotide polymorphisms (SNPs) associated with one carbon metabolism. We focused on two SNPs (rs1801394, MTRR 66 and rs1979227, SHMT1 1420) based on our earlier findings in astronauts (Zwart et al., FASEB J, 30:141–8, 2016). The 30-d bed rest began after collection of this sample. Optical coherence tomography images were collected before, during (days 15 and 30), and after (6 and 13 days after reambulation) bed rest, and the change in total retinal thickness (TRT) at various distances from Bruch's membrane opening (BMO) was evaluated against the number of MTRR A66G G alleles and SHMT1 C1420T C alleles. Results The change in TRT at various distances from the BMO in bed rest subjects exposed to mild hypercapnia and headward fluid shifts was strongly associated with the number of MTRR 66 G and SHMT1 1420 C alleles. Conclusions This finding may increase understanding of mechanisms involved in optic disc edema in astronauts and patients on Earth, and hence lead to development of targeted countermeasures. Funding Sources This work was funded by the NASA Human Health Countermeasures Element of the NASA Human Research Program.