Genotype, B-vitamin status, and androgens affect spaceflight-induced ophthalmic changes

Abstract

Ophthalmic changes have occurred in a subset of astronauts on International Space Station missions. Visual deterioration is considered the greatest human health risk of spaceflight. Affected astronauts exhibit higher concentrations of 1-carbon metabolites (e.g., homocysteine) before flight. We hypothesized that genetic variations in 1-carbon metabolism genes contribute to susceptibility to ophthalmic changes in astronauts. We investigated 5 polymorphisms in the methionine synthase reductase (MTRR), methylenetetrahydrofolate reductase (MTHFR), serine hydroxymethyltransferase (SHMT), and cystathionine β-synthase (CBS) genes and their association with ophthalmic changes after flight in 49 astronauts. The number of G alleles of MTRR 66 and C alleles of SHMT1 1420 both contributed to the odds of visual disturbances. Preflight dehydroepiandrosterone was positively associated with cotton wool spots, and serum testosterone response during flight was associated with refractive change. Block regression showed that B-vitamin status and genetics were significant predictors of many of the ophthalmic outcomes that we observed. In one example, genetics trended toward improving (P = 0.10) and B-vitamin status significantly improved (P < 0.001) the predictive model for refractive change after flight. We document an association between MTRR 66 and SHMT1 1420 polymorphisms and spaceflight-induced vision changes. This line of research could lead to therapeutic options for both space travelers and terrestrial patients.

© FASEB.

Figures

Figure 1.

Preflight DHEA-S tended to be associated with change in diopters in the eye with the biggest postflight change (n = 23) and with the incidence of cotton wool spots (P = 0.08 and P = 0.07, respectively). The increase in serum testosterone during flight (area under the curve) was related to the change in diopters after flight (n = 19). P < 0.05. Each symbol represents an individual value, and horizontal lines represent the mean and sd. Unadjusted P values are presented on each graph.

Figure 2.

MTRR and SHMT genotypes of astronauts with choroidal folds, cotton wool spots, and optic disc edema. Each point represents an individual astronaut. Significance of Somers' D association is indicated on each graph. Genotypes were merged (i.e., AG/GG) to ensure that the data are not identifiable.