Space Flight Ophthalmic Changes, Diet, and Vitamin Metabolism

Zwart, Sara R.; Gibson, Charles R.; Smith, Scott M.

doi:10.1016/b978-0-12-401717-7.00040-x

Cited by 8 publications

(5 citation statements)

References 27 publications

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“…Given that our results represent a cell state 48 h after the last radiation exposure this suggests a prolonged stress response and is strengthened by the evidence showing that radiation produces a persistent stress response in space radiation studies of mouse intestine [ 135 ]. Sustained systemic GC levels have been implicated in pathologies such as osteoporosis, myopathy, reduced serum vitamin D levels and cataracts [ 136 , 137 ] which are already known to occur in spaceflight [ 138 , 139 , 140 ]. This points to a role for radiation-induced GC levels being a contributing factor.…”

Section: Discussionmentioning

confidence: 99%

Induced Torpor as a Countermeasure for Low Dose Radiation Exposure in a Zebrafish Model

Cahill

Silveira

Renaud

et al. 2021

Cells

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The development of the Artemis programme with the goal of returning to the moon is spurring technology advances that will eventually take humans to Mars and herald a new era of interplanetary space travel. However, long-term space travel poses unique challenges including exposure to ionising radiation from galactic cosmic rays and potential solar particle events, exposure to microgravity and specific nutritional challenges arising from earth independent exploration. Ionising radiation is one of the major obstacles facing future space travel as it can generate oxidative stress and directly damage cellular structures such as DNA, in turn causing genomic instability, telomere shortening, extracellular-matrix remodelling and persistent inflammation. In the gastrointestinal tract (GIT) this can lead to leaky gut syndrome, perforations and motility issues, which impact GIT functionality and affect nutritional status. While current countermeasures such as shielding from the spacecraft can attenuate harmful biological effects, they produce harmful secondary particles that contribute to radiation exposure. We hypothesised that induction of a torpor-like state would confer a radioprotective effect given the evidence that hibernation extends survival times in irradiated squirrels compared to active controls. To test this hypothesis, a torpor-like state was induced in zebrafish using melatonin treatment and reduced temperature, and radiation exposure was administered twice over the course of 10 days. The protective effects of induced-torpor were assessed via RNA sequencing and qPCR of mRNA extracted from the GIT. Pathway and network analysis were performed on the transcriptomic data to characterise the genomic signatures in radiation, torpor and torpor + radiation groups. Phenotypic analyses revealed that melatonin and reduced temperature successfully induced a torpor-like state in zebrafish as shown by decreased metabolism and activity levels. Genomic analyses indicated that low dose radiation caused DNA damage and oxidative stress triggering a stress response, including steroidal signalling and changes to metabolism, and cell cycle arrest. Torpor attenuated the stress response through an increase in pro-survival signals, reduced oxidative stress via the oxygen effect and detection and removal of misfolded proteins. This proof-of-concept model provides compelling initial evidence for utilizing an induced torpor-like state as a potential countermeasure for radiation exposure.

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Section: Discussionmentioning

confidence: 99%

Induced Torpor as a Countermeasure for Low Dose Radiation Exposure in a Zebrafish Model

Cahill

Silveira

Renaud

et al. 2021

Cells

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“…Vitamin B 12 is inactivated by oxidation and, therefore, vitamin B 12 status in individuals with more oxidant risk factors is often low or low-normal (45). Unlike a decrease in serum folate, a decrease in circulating vitamin B 12 is not a generalized phenomenon for affected astronauts, but in some individual cases, circulating B 12 fluctuates or the metabolic indicator of cobalamin status, methylmalonic acid, is elevated during flight (unpublished results), which reflects vitamin B 12 insufficiency.…”

Section: Variations In Genetics Of Enzymes In the 1-carbon Metabolic mentioning

confidence: 99%

“…ISS cabin air also contains sources of formaldehyde that could contribute to formate production (70). Decreased status of folate or vitamin B 12 can increase plasma and urinary formate, as well. Formate is an intermediate of the 1-carbon pathway, and if B vitamin cofactors are not present in sufficient quantities to convert formate to 10-formyl tetrahydrofolate, then formate can build up in the plasma (71).…”

Section: Variations In Genetics Of Enzymes In the 1-carbon Metabolic mentioning

confidence: 99%

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Astronaut ophthalmic syndrome

Zwart¹,

Gibson²,

Gregory

et al. 2017

The FASEB Journal

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During and after missions on the International Space Station, some astronauts experience ophthalmic changes, including choroidal folds, optic disc edema, cotton-wool spots, globe flattening, and refraction changes. Astronauts with ophthalmic issues had significantly higher plasma concentrations of metabolites that are associated with the 1-carbon metabolic pathway than those without ophthalmic issues. We hypothesized that genetic differences might explain the metabolite differences. Indeed, genetics and B vitamin status were significant predictors of ophthalmic issues. We now have developed a hypothesis regarding the mechanisms that link 1-carbon pathway genetics and the condition that we suggest calling, "astronaut ophthalmic syndrome." We maintain that this condition is genetically predisposed and is associated with endothelial dysfunction that is induced by oxidative stress. Subsequent edema can hinder cerebrospinal fluid efflux and can lead to locally increased pressures in the subarachnoid space within the orbit, which impinges on the optic nerve and/or eye in affected individuals. Confirming this hypothesis will help characterize the genetics of 1-carbon pathway metabolism, homocysteine, oxidative stress, endothelial dysfunction, and cardiovascular and potentially other diseases.-Zwart, S. R., Gibson, C. R., Gregory, J. F., Mader, T. H., Stover, P. J., Zeisel, S. H., Smith, S. M. Astronaut ophthalmic syndrome.

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“…Astronauts with specific single nucleotide polymorphisms (SNPs) in one-carbon pathway genes, namely, the G allele for methionine synthase reductase (MTRR) A66G and the C allele for serine hydroxymethyltransferase (SHMT1) C1420T had a higher incidence of SANS pathologies (e.g., optic disc edema, globe flattening, choroidal folds) ( 5 , 6 ). The degree of optic disc edema in subjects exposed to head-down tilt bed rest (HDTBR) in a 0.5% CO 2 environment was higher in subjects with more G and C alleles (i.e., risk alleles) for MTRR 66 and SHMT1 1420, suggesting an association ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

Optic disc edema during strict 6° head-down tilt bed rest is related to one-carbon metabolism pathway genetics and optic cup volume

Zwart,

Macias,

Laurie

et al. 2023

Front. Ophthalmol.

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Some astronauts on International Space Station missions experience neuroophthalmological pathologies as part of spaceflight associated neuro-ocular syndrome (SANS). Strict head-down tilt bed rest (HDTBR) is a spaceflight analog that replicates SANS findings and those who had 3–4 risk alleles (G and C alleles from the methionine synthase reductase [MTRR] A66G and serine hydroxymethyltransferase [SHMT1] C1420T, respectively) as compared to 1-2 risk alleles, had a greater increase in total retinal thickness (TRT). The objective of this study was to identify factors that contribute to the individual variability of the development of SANS in a 60 d HDTBR at the German Aerospace Center’s:envihab facility, Cologne Germany. 22 of 24 subjects who participated in the HDTBR study provided blood samples for genetic analysis. Total retinal thickness and optic cup volume were measured before and after bed rest. Subjects with 3–4 versus 0-2 risk alleles had greater ΔTRT during and after bed rest, and the model improved with the addition of baseline optic cup volume. This bed rest study confirms that variants of MTRR and SHMT1 are associated with ocular pathologies. Subjects with more risk alleles had the greatest HDTBR-induced ΔTRT, reaffirming that genetics predispose some individuals to developing SANS. Preflight optic cup volume and genetics better predict ΔTRT than either one alone. Whether nutritional supplements can override the genetic influences on biochemistry, physiology, and pathophysiology remains to be tested. These findings have significant implications for both aerospace and terrestrial medicine.

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Space Flight Ophthalmic Changes, Diet, and Vitamin Metabolism

Cited by 8 publications

References 27 publications

Induced Torpor as a Countermeasure for Low Dose Radiation Exposure in a Zebrafish Model

Induced Torpor as a Countermeasure for Low Dose Radiation Exposure in a Zebrafish Model

Astronaut ophthalmic syndrome

Optic disc edema during strict 6° head-down tilt bed rest is related to one-carbon metabolism pathway genetics and optic cup volume

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