Menu

 

Task Book: Biological & Physical Sciences Division and Human Research Program
Advanced Search     

Project Title:  Risk of visual impairment and intracranial hypertension after space flight: Evaluation of the role of polymorphism of enzymes involved in one-carbon metabolism Reduce
Fiscal Year: FY 2015 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 03/15/2012  
End Date: 09/30/2015  
Task Last Updated: 10/02/2015 
Download report in PDF pdf
Principal Investigator/Affiliation:   Smith, Scott M Ph.D. / NASA Johnson Space Center 
Address:  Biomedical Research and Environmental Sciences Division/SK3 
2101 NASA Pkwy 
Houston , TX 77058-3607 
Email: scott.m.smith@nasa.gov 
Phone: 281-483-7204  
Congressional District: 36 
Web:  
Organization Type: NASA CENTER 
Organization Name: NASA Johnson Space Center 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Zwart, Sara  USRA/NASA Johnson Space Center 
Gregory, Jesse  University of Florida 
Ploutz-Snyder, Robert  USRA 
Key Personnel Changes / Previous PI: None
Project Information: Grant/Contract No. Directed Research 
Responsible Center: NASA JSC 
Grant Monitor: Norsk, Peter  
Center Contact:  
Peter.norsk@nasa.gov 
Solicitation / Funding Source: Directed Research 
Grant/Contract No.: Directed Research 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Nutrition:Risk of Inadequate Nutrition
(2) VIIP:Risk of Spaceflight-Induced Intracranial Hypertension/Vision Alterations (IRP Rev E)
Human Research Program Gaps: (1) N7.3:We need to identify the most important nutritional factors for ocular health (IRP Rev E)
(2) VIIP01:We do not know the etiological mechanisms and contributing risk factors for ocular structural and functional changes seen in-flight and postflight (IRP Rev E)
Flight Assignment/Project Notes: NOTE: End date changed to 09/30/2015 per PI (Ed., 10/9/14)

NOTE: End date changed to 10/01/2014 per PI (Ed., 04/10/2014)

NOTE: End date is 3/31/2014 per PI (Ed., 12/26/13)

NOTE: End date changed to 1/31/2014 per 6/27/13 HRP MTL information (Ed., 10/21/13)

Task Description: The occurrence of long-term or permanent changes in vision of International Space Station crew members during and after flight has been described as “the most significant clinical issue to date” for the U.S. space program. NASA has conducted 2 workshops in which the clinical issues were characterized as the presence of choroidal folds and occurrence of papilledema, significantly elevated opening pressures after lumbar puncture, and MRI (magnetic resonance imaging) visualization showing optic nerve swelling. A primary forward focus has been evaluation of intracranial hypertension and fluid shifts.

In evaluating data collected from the Nutritional Status Assessment Supplemental Medical Objective (SMO), we have identified elevations in 4 metabolites of the one-carbon metabolism pathway in affected crew members studied to date. These elevations and related data strongly suggest that polymorphism(s) of one or more of the enzymes in this pathway exist(s) in the affected crew members. 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 proposed study will accomplish this. We expect that, at a minimum, the results of the proposed effort will provide a guiding path for other research to be conducted that would allow this problem to be defined and resolved.

Rationale for HRP Directed Research: This research is directed because it contains highly constrained research, which requires focused and constrained data gathering and analysis that is more appropriately obtained through a non-competitive proposal.

Research Impact/Earth Benefits: We expect to find evidence of a relationship between polymorphism incidence, biochemical analytes, and vision and optic examination results in affected crew members. These results will guide the path for further research to define a clinical treatment plan for individuals developing symptoms during flight. The results of this effort may also have significant Earth-based applications, and may inform the understanding and treatment of idiopathic intracranial hypertension, migraine headaches, and other cerebrovascular issues.

Task Progress & Bibliography Information FY2015 
Task Progress: Seventy-four past, present, and future International Space Station (ISS) crewmembers were recruited to provide blood samples for biochemical, enzymatic, and limited genotype/polymorphism analyses. Genomic DNA prepared from peripheral leukocytes was analyzed for the existence of 5 single-nucleotide polymorphisms in the one-carbon metabolism pathway: 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C->T, MTHFR 1298A->T, serine hydroxymethyltransferase 1 (SHMT1) 1420C->T, cystathionine ß-synthase (CBS) 844ins68, and 5-methyltetrahydrofolate homocysteine methyltransferase reductase (MTRR) 66A->G. Data from vision and related eye exams was obtained, and we sought to relate those findings to the data from our study.

Study has been completed, results published – E-published in August 2015; expected final publication January 2016.

These findings document a genetic predisposition for some astronauts to develop VIIP (Vision Impairment and Intracranial Pressure) issues during flight. We have proposed a series of follow-on experiments to clarify and extend these findings. The implications of this research for one of NASA’s highest priority crew health risks are significant, along with the implications for a better understanding of the role of one-carbon metabolism in the health of the general population.

Bibliography Type: Description: (Last Updated: 05/25/2021)  Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Smith SM, Gregory JF, Zeisel SH, Ueland P, Gibson CR, Mader T, Kinchen JM, Ploutz-Snyder R, Zwart SR. "Vision issues and space flight: evaluation of one-carbon metabolism polymorphisms." Experimental Biology 2015, Boston, MA, March 28-April 1, 2015.

FASEB Journal. 2015 Apr;29(1 Suppl):134.1 See also http://www.fasebj.org/content/29/1_Supplement.toc for searching. , Apr-2015

Articles in Peer-reviewed Journals Zwart SR, Gregory JF, Zeisel SH, Gibson CR, Mader TH, Kinchen J, Ueland P, Ploutz-Snyder R, Heer M, Smith SM. "Genotype, B-vitamin status and androgens affect spaceflight-induced ophthalmic changes." FASEB J. 2016 Jan;30(1):141-8. Epub 2015 Aug 27. http://dx.doi.org/10.1096/fj.15-278457 ; PubMed PMID: 26316272; PubMed Central PMCID: PMC4684521 , Jan-2016
Books/Book Chapters Zwart SR, Gibson CR, Smith SM. "Space Flight Ophthalmic Changes, Diet, and Vitamin Metabolism." in "Handbook of Nutrition, Diet, and the Eye." Ed. V.R. Preedy. Waltham, MA : Academic Press, 2014. p. 393-399. ISBN: 978-0-12-401717-7. http://dx.doi.org/10.1016/B978-0-12-401717-7.00040-X , Apr-2014
Journal/Magazine covers Zwart SR, Gregory JF, Zeisel SH, Gibson CR, Mader TH, Kinchen J, Ueland P, Ploutz-Snyder R, Heer M, Smith SM. "Cover to be in published issue in January 2016 for 'Genotype, B-vitamin status and androgens affect spaceflight-induced ophthalmic changes.' " FASEB J. 2015 Aug 27. [Epub ahead of print] http://dx.doi.org/10.1096/fj.15-278457 ; PubMed PMID: 26316272; PubMed Central PMCID: PMC4684521 , Jan-2016
NASA Technical Documents Smith SM, Zwart SR, Heer MA. "Human Adaptation to Spaceflight: The Role of Nutrition (NP-2014-10-018-JSC)." Houston, TX: National Aeronautics and Space Administration Lyndon B. Johnson Space Center, 2014. (NP-2014-10-018-JSC) (ISBN 978-0-16-092629-7). Available through open access at: http://www.nasa.gov/hhp/education and http://www.nasa.gov/sites/default/files/human-adaptation-to-spaceflight-the-role-of-nutrition.pdf ; accessed 10/02/15. , Nov-2014
NASA Technical Documents Smith SM, Zwart SR, Douglas GL, Heer M. "Human adaptation to spaceflight: The role of food and nutrition. Second edition." Houston, TX: NASA Lyndon B. Johnson Space Center, 2021. 255 p. NP-2021-03-003-JSC. https://www.nasa.gov/sites/default/files/atoms/files/human_adaptation_2021_final.pdf , Apr-2021
Project Title:  Risk of visual impairment and intracranial hypertension after space flight: Evaluation of the role of polymorphism of enzymes involved in one-carbon metabolism Reduce
Fiscal Year: FY 2014 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 03/15/2012  
End Date: 09/30/2015  
Task Last Updated: 12/19/2013 
Download report in PDF pdf
Principal Investigator/Affiliation:   Smith, Scott M Ph.D. / NASA Johnson Space Center 
Address:  Biomedical Research and Environmental Sciences Division/SK3 
2101 NASA Pkwy 
Houston , TX 77058-3607 
Email: scott.m.smith@nasa.gov 
Phone: 281-483-7204  
Congressional District: 36 
Web:  
Organization Type: NASA CENTER 
Organization Name: NASA Johnson Space Center 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Zwart, Sara  USRA/NASA Johnson Space Center 
Gregory, Jesse  University of Florida 
Key Personnel Changes / Previous PI: None
Project Information: Grant/Contract No. Directed Research 
Responsible Center: NASA JSC 
Grant Monitor: Norsk, Peter  
Center Contact:  
Peter.norsk@nasa.gov 
Solicitation / Funding Source: Directed Research 
Grant/Contract No.: Directed Research 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Nutrition:Risk of Inadequate Nutrition
(2) VIIP:Risk of Spaceflight-Induced Intracranial Hypertension/Vision Alterations (IRP Rev E)
Human Research Program Gaps: (1) N7.3:We need to identify the most important nutritional factors for ocular health (IRP Rev E)
(2) VIIP01:We do not know the etiological mechanisms and contributing risk factors for ocular structural and functional changes seen in-flight and postflight (IRP Rev E)
Flight Assignment/Project Notes: NOTE: End date changed to 09/30/2015 per PI (Ed., 10/9/14)

NOTE: End date changed to 10/01/2014 per PI (Ed., 04/10/2014)

NOTE: End date is 3/31/2014 per PI (Ed., 12/26/13)

NOTE: End date changed to 1/31/2014 per 6/27/13 HRP MTL information (Ed., 10/21/13)

Task Description: The occurrence of long-term or permanent changes in vision of International Space Station crew members during and after flight has been described as “the most significant clinical issue to date” for the U.S. space program. NASA has conducted 2 workshops in which the clinical issues were characterized as the presence of choroidal folds and occurrence of papilledema, significantly elevated opening pressures after lumbar puncture, and MRI visualization showing optic nerve swelling. A primary forward focus has been evaluation of intracranial hypertension and fluid shifts.

In evaluating data collected from the Nutritional Status Assessment Supplemental Medical Objective (SMO), we have identified elevations in 4 metabolites of the one-carbon metabolism pathway in affected crew members studied to date. These elevations and related data strongly suggest that polymorphism(s) of one or more of the enzymes in this pathway exist(s) in the affected crew members. 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 proposed study will accomplish this. We expect that, at a minimum, the results of the proposed effort will provide a guiding path for other research to be conducted that would allow this problem to be defined and resolved.

Rationale for HRP Directed Research: This research is directed because it contains highly constrained research, which requires focused and constrained data gathering and analysis that is more appropriately obtained through a non-competitive proposal.

Research Impact/Earth Benefits: We expect to find evidence of a relationship between polymorphism incidence, biochemical analytes, and vision and optic examination results in affected crew members. These results will guide the path for further research to define a clinical treatment plan for individuals developing symptoms during flight. The results of this effort may also have significant Earth-based applications, and may inform the understanding and treatment of idiopathic intracranial hypertension, migraine headaches, and other cerebrovascular issues.

Task Progress & Bibliography Information FY2014 
Task Progress: Recruiting was completed in August 2013, with 70 of a potential 72 USOS crewmembers participating in the experiment. Samples analyses were analyzed in 1-2 batches, and were completed in late 2013. Working to obtain medical record data to complete analyses.

Bibliography Type: Description: (Last Updated: 05/25/2021)  Show Cumulative Bibliography Listing
 
 None in FY 2014
Project Title:  Risk of visual impairment and intracranial hypertension after space flight: Evaluation of the role of polymorphism of enzymes involved in one-carbon metabolism Reduce
Fiscal Year: FY 2013 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 03/15/2012  
End Date: 01/31/2014  
Task Last Updated: 12/17/2012 
Download report in PDF pdf
Principal Investigator/Affiliation:   Smith, Scott M Ph.D. / NASA Johnson Space Center 
Address:  Biomedical Research and Environmental Sciences Division/SK3 
2101 NASA Pkwy 
Houston , TX 77058-3607 
Email: scott.m.smith@nasa.gov 
Phone: 281-483-7204  
Congressional District: 36 
Web:  
Organization Type: NASA CENTER 
Organization Name: NASA Johnson Space Center 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Zwart, Sara  USRA/NASA Johnson Space Center 
Gregory, Jesse  University of Florida 
Key Personnel Changes / Previous PI: None
Project Information: Grant/Contract No. Directed Research 
Responsible Center: NASA JSC 
Grant Monitor: Norsk, Peter  
Center Contact:  
Peter.norsk@nasa.gov 
Solicitation / Funding Source: Directed Research 
Grant/Contract No.: Directed Research 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Nutrition:Risk of Inadequate Nutrition
(2) VIIP:Risk of Spaceflight-Induced Intracranial Hypertension/Vision Alterations (IRP Rev E)
Human Research Program Gaps: (1) N7.3:We need to identify the most important nutritional factors for ocular health (IRP Rev E)
(2) VIIP01:We do not know the etiological mechanisms and contributing risk factors for ocular structural and functional changes seen in-flight and postflight (IRP Rev E)
Flight Assignment/Project Notes: NOTE: End date changed to 1/31/2014 per 6/27/13 HRP MTL information (Ed., 10/21/13)

Task Description: The occurrence of long-term or permanent changes in vision of International Space Station crew members during and after flight has been described as “the most significant clinical issue to date” for the U.S. space program. NASA has conducted 2 workshops in which the clinical issues were characterized as the presence of choroidal folds and occurrence of papilledema, significantly elevated opening pressures after lumbar puncture, and MRI visualization showing optic nerve swelling. A primary forward focus has been evaluation of intracranial hypertension and fluid shifts.

In evaluating data collected from the Nutritional Status Assessment Supplemental Medical Objective (SMO), we have identified elevations in 4 metabolites of the one-carbon metabolism pathway in affected crew members studied to date. These elevations and related data strongly suggest that polymorphism(s) of one or more of the enzymes in this pathway exist(s) in the affected crew members. 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 proposed study will accomplish this. We expect that, at a minimum, the results of the proposed effort will provide a guiding path for other research to be conducted that would allow this problem to be defined and resolved.

Rationale for HRP Directed Research: This research is directed because it contains highly constrained research, which requires focused and constrained data gathering and analysis that is more appropriately obtained through a non-competitive proposal.

Research Impact/Earth Benefits: We expect to find evidence of a relationship between polymorphism incidence, biochemical analytes, and vision and optic examination results in affected crew members. These results will guide the path for further research to define a clinical treatment plan for individuals developing symptoms during flight. The results of this effort may also have significant Earth-based applications, and may inform the understanding and treatment of idiopathic intracranial hypertension, migraine headaches, and other cerebrovascular issues.

Task Progress & Bibliography Information FY2013 
Task Progress: Project approval was granted on March 15, 2012. IRB approval obtained on April 19. Initial crew briefings and data collections started on April 30, 2012. There were some delays with several facets of study implementation, including: establishing protocols for contacting crewmembers, obtaining ESA and JAXA Medical Board approvals (received in September, 2012), and then in gaining IRB and ESA Medical Board approval for use of a multilateral consent form (as opposed to the NASA consent form, ongoing as of this writing). Nonetheless, recruiting has been ongoing and will continue through the project period. Samples are being analyzed in batches, and thus no data are available yet.

Bibliography Type: Description: (Last Updated: 05/25/2021)  Show Cumulative Bibliography Listing
 
Books/Book Chapters Zwart SR, Gibson CR, Smith SM. "Space flight opthalmic changes, diet, and vitamin metabolism." in "Handbook of Nutrition, Diet, and the Eye." Ed. V.R. Preedy. Waltham, MA : Academic Press, In press, as of December 2012., Dec-2012
Project Title:  Risk of visual impairment and intracranial hypertension after space flight: Evaluation of the role of polymorphism of enzymes involved in one-carbon metabolism Reduce
Fiscal Year: FY 2012 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 03/15/2012  
End Date: 09/30/2013  
Task Last Updated: 04/05/2012 
Download report in PDF pdf
Principal Investigator/Affiliation:   Smith, Scott M Ph.D. / NASA Johnson Space Center 
Address:  Biomedical Research and Environmental Sciences Division/SK3 
2101 NASA Pkwy 
Houston , TX 77058-3607 
Email: scott.m.smith@nasa.gov 
Phone: 281-483-7204  
Congressional District: 36 
Web:  
Organization Type: NASA CENTER 
Organization Name: NASA Johnson Space Center 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Zwart, Sara  USRA/NASA Johnson Space Center 
Gregory, Jesse  University of Florida 
Project Information: Grant/Contract No. Directed Research 
Responsible Center: NASA JSC 
Grant Monitor: Norsk, Peter  
Center Contact:  
Peter.norsk@nasa.gov 
Solicitation / Funding Source: Directed Research 
Grant/Contract No.: Directed Research 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Nutrition:Risk of Inadequate Nutrition
(2) VIIP:Risk of Spaceflight-Induced Intracranial Hypertension/Vision Alterations (IRP Rev E)
Human Research Program Gaps: (1) N7.3:We need to identify the most important nutritional factors for ocular health (IRP Rev E)
(2) VIIP01:We do not know the etiological mechanisms and contributing risk factors for ocular structural and functional changes seen in-flight and postflight (IRP Rev E)
Task Description: The occurrence of long-term or permanent changes in vision of International Space Station crew members during and after flight has been described as “the most significant clinical issue to date” for the U.S. space program. NASA has conducted 2 workshops in which the clinical issues were characterized as the presence of choroidal folds and occurrence of papilledema, significantly elevated opening pressures after lumbar puncture, and MRI visualization showing optic nerve swelling. A primary forward focus has been evaluation of intracranial hypertension and fluid shifts.

In evaluating data collected from the Nutritional Status Assessment Supplemental Medical Objective (SMO), we have identified elevations in 4 metabolites of the one-carbon metabolism pathway in affected crew members studied to date. These elevations and related data strongly suggest that polymorphism(s) of one or more of the enzymes in this pathway exist(s) in the affected crew members. 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 proposed study will accomplish this. We expect that, at a minimum, the results of the proposed effort will provide a guiding path for other research to be conducted that would allow this problem to be defined and resolved.

Rationale for HRP Directed Research: This research is directed because it contains highly constrained research, which requires focused and constrained data gathering and analysis that is more appropriately obtained through a non-competitive proposal.

Research Impact/Earth Benefits: 0

Task Progress & Bibliography Information FY2012 
Task Progress: New project for FY2012.

Bibliography Type: Description: (Last Updated: 05/25/2021)  Show Cumulative Bibliography Listing
 
 None in FY 2012