Risk of visual impairment and intracranial hypertension after space flight: Evaluation of the role of polymorphism of enzymes involved in one-carbon metabolism (One Carbon) - 08.29.18

Overview | Description | Applications | Operations | Results | Publications | Imagery

ISS Science for Everyone

Science Objectives for Everyone
Some crewmembers return from ISS missions with altered vision and other related ocular issues.  Preliminary data suggests that there may be a predisposition for the crewmembers that had vision issues, evidenced by differences in blood chemistry, to have been more susceptible to these changes.  This study is designed to look at specific genetic markers that could explain these blood chemistry differences, to see if or how that relates to the vision changes in astronauts.
Science Results for Everyone
Information Pending

The following content was provided by Scott M. Smith, Ph.D., and is maintained in a database by the ISS Program Science Office.
Experiment Details

OpNom:

Principal Investigator(s)
Scott M. Smith, Ph.D., NASA Johnson Space Center, Houston, TX, United States

Co-Investigator(s)/Collaborator(s)
Sara R. Zwart, Ph.D., University of Texas Medical Branch, Houston, TX, United States
Jesse F. Gregory III, Ph.D., University of Florida, Gainesville, FL, United States
Robert J. Ploutz-Snyder, Ph.D., University of Michigan School of Nursing, Ann Arbor, MI, United States

Developer(s)
NASA Johnson Space Center, Human Research Program, ISS Medical Project, Houston, TX, United States

Sponsoring Space Agency
National Aeronautics and Space Administration (NASA)

Sponsoring Organization
Human Exploration and Operations Mission Directorate (HEOMD)

Research Benefits
Information Pending

ISS Expedition Duration


Expeditions Assigned
Information Pending

Previous Missions
Information Pending

^ back to top

Experiment Description

Research Overview

Recently identified vision issues in some astronauts are a significant risk for human space travelers. While a primary forward focus has been evaluation of intracranial hypertension and fluid shifts, preliminary data from the Nutritional Status Assessment project identified biochemical changes in markers of the “one carbon metabolism” pathway. These changes strongly suggest that polymorphism(s) of one or more of the enzymes in this pathway exist(s) in the crewmembers experiencing vision issues. The incidence of such polymorphisms in the general population is relatively high, and they have been associated on Earth with increased risk of stroke and other cardiovascular, and specifically cerebrovascular, events. Therefore it is within the realm of plausibility, given the number and ethnic background of the affected astronauts, that these polymorphisms could be causing the cerebrovascular and optical medical issues in astronauts. This evidence demands follow-up to more clearly define this relationship.

The evidence described above is essentially circumstantial evidence, as no genetic data were collected in the earlier study.  The current study will determine several polymorphisms, along with an extended biochemistry profile of one carbon and related metabolites. These data will be related to vision and other ophthalmologic findings in ISS crews, along with information about cabin environment and other mission related data.  The study aims to collect data on all USOS ISS crewmembers, past, present, and future.

The data may help better understand the vision issues of spaceflight, and may have implications for further research in this area and/or treatment options.

Description
Recently identified vision issues in some astronauts are a significant risk for human space travelers. While a primary forward focus has been evaluation of intracranial hypertension and fluid shifts, preliminary data from the Nutritional Status Assessment project identified biochemical changes in markers of the “one carbon metabolism” pathway. Among these changes were significantly elevated concentrations of four one carbon metabolites (homocysteine, methylmalonic acid, 2-methylcitric acid, and cystathionine) in crewmembers that experienced vision issues, compared to those that did not have vision issues.  Perhaps most striking, these changes existed before flight.
 
Several potentially confounding factors (e.g., vitamin status, coffee consumption) were ruled out as a cause of these changes. While folate status was normal in all of these individuals (estimated with red blood cell folate concentration), the serum folate levels were significantly lower in crewmembers with vision issues.

When combined, these differences strongly suggest that polymorphism(s) of one or more of the enzymes in this pathway exist(s) in the crewmembers experiencing vision issues. Polymorphisms are simply multiple forms of the enzymes that occur in the population.  The incidence of such polymorphisms in the general population is relatively high (in some cases more than 20% of all people have specific forms of the enzymes).
 
These one carbon pathway polymorphisms have been associated on Earth with increased risk of stroke and other cardiovascular, and specifically cerebrovascular, events. Therefore it is within the realm of plausibility, given the number and ethnic background of the affected astronauts, that these polymorphisms could be causing the cerebrovascular and optical medical issues in astronauts.

This evidence demands follow-up to more clearly define this relationship. The evidence described above is essentially circumstantial evidence, as no genetic data were collected in the earlier study.  The current study will determine several polymorphisms, along with an extended biochemistry profile of one carbon and related metabolites.

These data will be related to vision and other ophthalmologic findings in ISS crews, along with information about cabin environment and other mission related data.  The study aims to collect data on all USOS ISS crewmembers, past, present, and future. The data may help better understand the vision issues of spaceflight, and may have implications for further research in this area and/or treatment options.

^ back to top

Applications

Space Applications
The results of this study may provide a guiding path for other research to be conducted that would allow the vision problem to be defined and resolved.

Earth Applications
Given that one carbon polymorphisms have been associated in the general population with an increased incidence of cerebrovascular issues, like stroke and migraine, there is potential benefit of the study findings to the medical, scientific, and general communities. 

^ back to top

Operations

Operational Requirements and Protocols

This is a unique study that requires only a fasting blood sample collection at any time, before or after flight.
 
None, this is a ground-based study

^ back to top

Decadal Survey Recommendations

Information Pending

^ back to top

Results/More Information

Information Pending

^ back to top

Results Publications

    Zwart SR, Gibson CR, Mader TH, Ericson K, Ploutz-Snyder RJ, Heer MA, Smith SM.  Vision Changes After Spaceflight Are Related to Alterations in Folate- and Vitamin B-12-Dependent One-Carbon Metabolism. Journal of Nutrition. 2012 Mar 1; 142(3): 427-431. DOI: 10.3945/jn.111.154245. PMID: 22298570.

    Zwart SR, Gregory III JF, Zeisel SH, Gibson CR, Mader TH, Kinchen JM, Ueland PM, Ploutz-Snyder RJ, Heer MA, Smith SM.  Genotype, B-vitamin status, and androgens affect space flight-induced ophthalmic changes. FASEB: Federation of American Societies for Experimental Biology Journal. 2016 January; 30(1): 141-148. DOI: 10.1096/fj.15-278457. PMID: 26316272.

^ back to top

Ground Based Results Publications

^ back to top

ISS Patents

^ back to top

Related Publications

    Zwart SR, Gibson CR, Gregory III JF, Mader TH, Stover PJ, Zeisel SH, Smith SM.  Astronaut ophthalmic syndrome. FASEB: Federation of American Societies for Experimental Biology Journal. 2017 September; 31(9): 3746–3756. DOI: 10.1096/fj.201700294.

^ back to top

Related Websites
New Findings on Astronaut Vision Loss

^ back to top


Imagery

image

A graphical depiction of the One Carbon study, highlighting the eye, DNA, and the concept that a single base pair change in the DNA may be involved in the vision issues of spaceflight.  This has implications for ISS astronauts, as well as for future exploration missions, alluded to with the Hubble image in the background.


+ View Larger Image