Association of Genetics and B Vitamin Status With the Magnitude of Optic Disc Edema During 30-Day Strict Head-Down Tilt Bed Rest

Zwart, Sara R.; Laurie, Steven S.; Chen, John J.; Macias, Brandon R.; Lee, Stuart M. C.; Stenger, Michael B.; Grantham, Bart; Carey, Knox; Young, Millennia; Smith, Scott M.

doi:10.1001/jamaophthalmol.2019.3124

Cited by 36 publications

(56 citation statements)

References 14 publications

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“…A genetic predisposition to optic disc edema development has been identified in the SANS subgroup of this study 12,13 as well as in astronauts who develop SANS 46 . Low levels of B-vitamins (B 6 , B 12 , and folate) and 1-carbon pathway risk alleles (linked to homocysteine levels) predict optic disc edema during HDBR+CO 2 12,13 and spaceflight 14,15 . In healthy older adults, lower levels of vitamin B 12 and high levels of homocysteine are associated with greater whole brain 47 and cerebral white matter atrophy 48 , respectively.…”

Section: Discussionmentioning

confidence: 58%

“…In healthy older adults, lower levels of vitamin B 12 and high levels of homocysteine are associated with greater whole brain 47 and cerebral white matter atrophy 48 , respectively. It is thus feasible that subgroup differences in B vitamin levels and risk alleles in the current study 12,13 contribute to the structural connectivity differences at baseline. As there exists a close correspondence between brain structural connectivity and functional connectivity 49 , it is possible that the observed pre-bed rest FC differences may arise from subgroup differences in structural connectivity within the identified networks.…”

Section: Discussionmentioning

confidence: 95%

“…We show that the SANS subgroup exhibited a distinct pattern of resting-state connectivity changes involving visual and vestibular brain regions during the HDBR+CO 2 intervention. Recent work has shown that genetic and B vitamin status are predictors of optic disc edema development during this HDBR+CO 2 intervention 12,13 , and during spaceflight 14,15 . In light of this, we further investigated resting-state connectivity differences between the SANS and NoSANS subgroup prior to bed rest.…”

Section: Introductionmentioning

confidence: 95%

“…In order to better replicate the ISS environment, NASA conducted the current study employing 30 days of strict HDBR in 0.5% ambient CO 2 (HDBR+CO 2 ). A subset of participants developed optic disc edema -- a sign of SANS -- by the end of the intervention 3,11,12 . These ophthalmic findings have been described in detail elsewhere 11,12 .…”

Section: Introductionmentioning

confidence: 99%

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Ophthalmic Changes in a Spaceflight Analog Are Associated with Brain Functional Reorganization

McGregor

Lee

Mulder

et al. 2020

Preprint

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ImportanceFollowing long-duration missions onboard the International Space Station, some astronauts develop ophthalmic abnormalities collectively referred to as Spaceflight Associated Neuro-ocular Syndrome (SANS). Optic disc edema is a common sign of SANS. SANS presents significant potential risk to astronaut health and performance; however, the origin and effects of SANS are not understood as signs of SANS have not manifested in previous spaceflight analog studies.ObjectiveTo investigate whether development of optic disc edema during a spaceflight analog impacts resting-state functional connectivity.Design, Setting and ParticipantsEleven healthy volunteers participated in this 58-day longitudinal study conducted at the :envihab facility at the German Aerospace Center.Interventions or ExposuresBaseline data were collected during a 14-day ambulatory phase in standard ambient air. All participants then underwent a spaceflight analog intervention: 30 days of strict head-down tilt bed rest in elevated ambient carbon dioxide (HDBR+CO2). The elevated CO2 level (0.5%) was matched to the hypercapnic environment of the International Space Station. The intervention was followed by a 14-day ambulatory recovery phase in standard ambient air. During the HDBR+CO2 spaceflight analog, 5 participants developed optic disc edema (SANS subgroup) and 6 did not (NoSANS group).Main Outcomes and MeasuresUsing functional magnetic resonance imaging (fMRI), we acquired resting-state data at 6 time points throughout the study: before (2), during (2), and after (2) the HDBR+CO2 intervention. We assessed the time course of resting-state functional connectivity changes from before, during, to after the HDBR+CO2, and contrasted longitudinal changes between the SANS and NoSANS subgroups. We also assessed if the SANS and NoSANS subgroups exhibited differential patterns of resting-state functional connectivity prior to the HDBR+CO2 intervention.ResultsThe SANS and NoSANS subgroups exhibited differential patterns of resting-state connectivity changes during the HDBR+CO2 spaceflight analog within visual and vestibular-related brain networks. We further found that the SANS and NoSANS subgroups exhibited differential resting-state brain activity prior to the spaceflight analog within a visual cortical network and within a large-scale network of brain areas involved in multisensory integration.Conclusions and RelevanceSubgroup differences in resting-state functional connectivity changes may reflect differential patterns of visual and vestibular reweighting as optic disc edema develops during the HDBR+CO2 spaceflight analog. This finding suggests that SANS impacts not only neuro-ocular structures, but also brain function. Future prospective investigations incorporating sensory assessments are required to determine the functional significance of the observed connectivity differences.KEY POINTSQuestionDoes optic disc edema development during head-down tilt bed rest with elevated carbon dioxide impact brain resting-state functional connectivity?FindingsA subset of participants developed optic disc edema during the head-down tilt bed rest intervention with elevated ambient CO2. Participants who developed optic disc edema exhibited a distinct pattern of resting-state functional connectivity changes within visual and vestibular-related networks during the spaceflight analog compared to participants who did not. Participants who developed optic disc edema exhibited different resting-state brain activity prior to the spaceflight analog within a visual cortical network and within a large-scale network of brain areas involved in multisensory integration.MeaningDevelopment of optic disc edema was associated with distinct patterns of brain resting-state functional connectivity during and prior to the spaceflight analog.

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Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

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Ophthalmic Changes in a Spaceflight Analog Are Associated with Brain Functional Reorganization

McGregor

Lee

Mulder

et al. 2020

Preprint

Self Cite

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“…Elevated intracranial pressure (ICP) has been postulated to be a contributing factor to SANS, but so far there are no supporting data for this proposed mechanism, and astronauts typically report few or no symptoms (e.g., headaches) associated with elevated ICP (Laurie et al, 2020;Lawley et al, 2017). On the other hand, both spaceflight and strict head-down tilt bed rest have documented cases of optic disc edema (Laurie et al, 2020), and altered one-carbon metabolism has been associated with ocular changes in both of these models (Zwart et al, 2019). Recent studies indicate that some of the biology that might be responsible for SANS is related to the mitochondrial dysfunction and oxidative stress from systemic responses (da Silveira et al, 2020).…”

Section: Space-associated Neuro-ocular Syndromementioning

confidence: 99%

Fundamental Biological Features of Spaceflight: Advancing the Field to Enable Deep-Space Exploration

Afshinnekoo

Scott

MacKay

et al. 2020

Cell

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261

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Research on astronaut health and model organisms have revealed six features of spaceflight biology that guide our current understanding of fundamental molecular changes that occur during space travel. The features include oxidative stress, DNA damage, mitochondrial dysregulation, epigenetic changes (including gene regulation), telomere length alterations, and microbiome shifts. Here we review the known hazards of human spaceflight, how spaceflight affects living systems through these six fundamental features, and the associated health risks of space exploration. We also discuss the essential issues related to the health and safety of astronauts involved in future missions, especially planned long-duration and Martian missions.

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Optic Disc Edema and Choroidal Engorgement in Astronauts During Spaceflight and Individuals Exposed to Bed Rest

et al. 2020

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IMPORTANCE Optic disc edema develops in astronauts during long-duration spaceflight and is a risk for all future astronauts during spaceflight. Having a ground-based analogue of weightlessness that reproduces critical features of spaceflight-associated neuro-ocular syndrome will facilitate understanding, preventing, and/or treating this syndrome. OBJECTIVE To determine whether the ocular changes in individuals exposed to an analogue of weightlessness are similar to the ocular changes in astronauts exposed to a duration of spaceflight comparable to this analogue of weightlessness. DESIGN, SETTING, AND PARTICIPANTS This cohort study, conducted from 2012 to 2018, investigated 11 healthy test participants before, during, and after 30 days of strict 6°h ead-down tilt bed rest as well as 20 astronauts before and during approximately 30 days of spaceflight. Data were collected at NASA Johnson Space Center, the German Aerospace Center, and on board the International Space Station. Statistical analysis was performed from February 13 to April 24, 2019. MAIN OUTCOMES AND MEASURES Peripapillary total retinal thickness and peripapillary choroid thickness quantified from optical coherence tomography images. RESULTS Peripapillary total retinal thickness increased to a greater degree among 11 individuals (6 men and 5 women; mean [SD] age, 33.4 [8.0 years]) exposed to bed rest than among 20 astronauts (17 men and 3 women; mean [SD] age, 46.0 [6.0] years), with a mean difference between groups of 37 μm (95% CI, 13-61 μm; P = .005). Conversely, choroid thickness did not increase among the individuals exposed to bed rest but increased among the astronauts, resulting in a mean difference between groups of 27 μm (95% CI, 14-41 μm; P < .001). CONCLUSIONS AND RELEVANCE These findings suggest that strict head-down tilt bed rest produces a different magnitude of edema than occurs after a similar duration of spaceflight, and no change in choroid thickness. It is possible that a mild, long-term elevation in intracranial pressure experienced by individuals exposed to bed rest is greater than the intracranial pressure experienced by astronauts during spaceflight, which may explain the different severity of optic disc edema between the cohorts. Gravitational gradients that remain present during bed rest may explain the lack of increase in choroid thickness during bed rest, which differs from the lack of gravitational gradients during spaceflight. Despite the possibility that different mechanisms may underlie optic disc edema development in modeled and real spaceflight, use of this terrestrial model of spaceflight-associated neuro-ocular syndrome will be assistive in the development of effective countermeasures that will protect the eyes of astronauts during future space missions.

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Association of Genetics and B Vitamin Status With the Magnitude of Optic Disc Edema During 30-Day Strict Head-Down Tilt Bed Rest

Cited by 36 publications

References 14 publications

Ophthalmic Changes in a Spaceflight Analog Are Associated with Brain Functional Reorganization

Ophthalmic Changes in a Spaceflight Analog Are Associated with Brain Functional Reorganization

Fundamental Biological Features of Spaceflight: Advancing the Field to Enable Deep-Space Exploration

Optic Disc Edema and Choroidal Engorgement in Astronauts During Spaceflight and Individuals Exposed to Bed Rest

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