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All sourcesNASA NTRSDOE OSTI
NASA NTRSDate not supplied

MULTI-OMICS STUDY OF THE EFFECT OF REDOX-ACTIVE METALLOPORPHYRIN ON MURINE RETINA DURING SPACEFLIGHT

Astronauts returning from spaceflight have experienced eye problems, which may decrease retinal performance and lead to long-term effects on visual acuity. This study leverages the collected data from spaceflown murine retinas that were treated with redox-active metalloporphyrin (BuOE) to mitigate spaceflight-induced changes and respective ground controls. 10-week-old adult C57BL/6 male mice (n=5 in each of BuOE treated and saline control groups for spaceflown and ground control samples) were flown on Space-X 24 to the ISS national lab, kept in low earth orbit for 35 days and returned to Earth alive. Our multi-omics analysis of RNA-sequencing and reduced representation bisulfite sequencing (RRBS) data generated from subsequent murine retina tissues uncovered genes, pathways, and epigenetic modifications consistent with therapeutic potential of BuOE. From RNA-Seq analysis of spaceflown murine samples, the treatment group show differentially expressed genes relative to saline controls that reached significance (adjusted p-value < 0.05) and included genes Gpx3 and Crhbp, which are related to protection against cell oxidative damage and cellular response to organonitrogen compounds. Ranked fold-changes from the same contrast were used for gene set enrichment analysis, which showed biological processes reaching significance (adjusted p-value < 0.05) including glutathione metabolic processes and cellular response to xenobiotic stimulus. RRBS data of the spaceflown murine samples found 139 hyper or hypo differentially methylated sites spread across chromosomes 1-19 (20% promoters, 21% exons, 43% introns | 20 CpG islands, 7 CpG shores) with a 10% methylation difference (q-value < 0.05).The findings from this investigation have the potential to provide valuable insights into the molecular mechanisms underlying conditions like spaceflight associated neuro-ocular syndrome and assess the effectiveness of BuOE as a countermeasure for astronauts experiencing neuro-ophthalmic abnormalities, which can lead to long-term effects on visual acuity.

Biostatistics↗
NASA NTRS2024

Multi-Omics Study of the Effect of Redox-Active Metalloporphyrin on Murine Retina During Spaceflight

Astronauts returning from spaceflight have experienced eye problems, which may decrease retinal performance and lead to long-term effects on visual acuity. This study leverages the collected data from spaceflown murine retinas that were treated with redox-active metalloporphyrin (BuOE) to mitigate spaceflight-induced changes and respective ground controls. 10-week-old adult C57BL/6 male mice (n=5 in each of BuOE treated and saline control groups for spaceflown and ground control samples) were flown on Space-X 24 to the ISS national lab, kept in low earth orbit for 35 days and returned to Earth alive. Our multi-omics analysis of RNA-sequencing and reduced representation bisulfite sequencing (RRBS) data generated from subsequent murine retina tissues uncovered genes, pathways, and epigenetic modifications consistent with therapeutic potential of BuOE. From RNA-Seq analysis of spaceflown murine samples, the treatment group show differentially expressed genes relative to saline controls that reached significance (adjusted p-value < 0.05) and included genes Gpx3 and Crhbp, which are related to protection against cell oxidative damage and cellular response to organonitrogen compounds. Ranked fold-changes from the same contrast were used for gene set enrichment analysis, which showed biological processes reaching significance (adjusted p-value < 0.05) including glutathione metabolic processes and cellular response to xenobiotic stimulus. RRBS data of the spaceflown murine samples found 139 hyper or hypo differentially methylated sites spread across chromosomes 1-19 (20% promoters, 21% exons, 43% introns | 20 CpG islands, 7 CpG shores) with a 10% methylation difference (q-value < 0.05).The findings from this investigation have the potential to provide valuable insights into the molecular mechanisms underlying conditions like spaceflight associated neuro-ocular syndrome and assess the effectiveness of BuOE as a countermeasure for astronauts experiencing neuro-ophthalmic abnormalities, which can lead to long-term effects on visual acuity.

Biostatistics↗
NASA NTRS2016

Microgravity-Induced Physiological Fluid Redistribution: Computational Analysis to Assess Influence of Physiological Parameters

Space flight impacts human physiology in many ways, the most immediate being the marked cephalad (headward) shift of fluid upon introduction into the microgravity environment. This physiological response to microgravity points to the redistribution of blood and interstitial fluid as a major factor in the loss of venous tone and reduction in heart muscle efficiency which impact astronaut performance. In addition, researchers have hypothesized that a reduction in astronaut visual acuity, part of the Visual Impairment and Intracranial Pressure (VIIP) syndrome, is associated with this redistribution of fluid. VIIP arises within several months of beginning space flight and includes a variety of ophthalmic changes including posterior globe flattening, distension of the optic nerve sheath, and kinking of the optic nerve. We utilize a suite of lumped parameter models to simulate microgravity-induced fluid redistribution in the cardiovascular, central nervous and ocular systems to provide initial and boundary data to a 3D finite element simulation of ocular biomechanics in VIIP. Specifically, the lumped parameter cardiovascular model acts as the primary means of establishing how microgravity, and the associated lack of hydrostatic gradient, impacts fluid redistribution. The cardiovascular model consists of 16 compartments, including three cerebrospinal fluid (CSF) compartments, three cranial blood compartments, and 10 thoracic and lower limb blood compartments. To assess the models capability to address variations in physiological parameters, we completed a formal uncertainty and sensitivity analysis that evaluated the relative importance of 42 input parameters required in the model on relative compartment flows and compartment pressures. Utilizing the model in a pulsatile flow configuration, the sensitivity analysis identified the ten parameters that most influenced each compartment pressure. Generally, each compartment responded appropriately to parameter variations associated with itself and adjacent compartments. However, several unexpected interactions between components, such as between the choroid plexus and the lower capillaries, were found, and are due to simplifications in the formulation of the model. The analysis illustrates that highly influential parameters and those that have unique influences within the model formulation must be tightly controlled for successful model application.

gravitational physiology↗
NASA NTRS2017

Modeling Microgravity Induced Fluid Redistribution Autoregulatory and Hydrostatic Enhancements

Space flight induces a marked cephalad (headward) redistribution of blood and interstitial fluid potentially resulting in a loss of venous tone and reduction in heart muscle efficiency upon introduction into the microgravity environment. Using various types of computational models, we are investigating how this fluid redistribution may induce intracranial pressure changes, relevant to reported reductions in astronaut visual acuity, part of the Visual Impairment and Intracranial Pressure (VIIP) syndrome. Methods: We utilize a lumped parameter cardiovascular system (CVS) model, augmented by compartments comprising the cerebral spinal fluid (CSF) space, as the primary tool to describe how microgravity, and the associated lack of hydrostatic gradient, impacts fluid redistribution. Models of ocular fluid pressures and biomechanics then accept the output of the above model as boundary condition input to allow more detailed, local analysis (see IWS Abstract by Ethier et al.). Recently, we enhanced the capabilities our previously reported CVS model through the implementation of robust autoregulatory mechanisms and a more fundamental approach to the implementation of hydrostatic mechanisms. Modifying the approach of Blanco et al., we implemented auto-regulation in a quasi-static manner, as an averaged effect across the span of one heartbeat. This approach reduced the higher frequency perturbations from the regulatory mechanism and was intended to allow longer simulation times (days) than models that implement within-beat regulatory mechanisms (minutes). A more fundamental approach to hydrostatics was implemented by a quasi-1D approach, in which compartment descriptions include compartment length, orientation and relative position, allowed for modeling of body orientation, relative body positioning and, in the future, alternative gravity environments. At this time the inclusion of hydrostatic mechanisms supplies additional capabilities to train and validate the CVS model with terrestrial data. Results and Conclusions: With the implementation of auto-regulation and hydrostatic modeling capabilities, the model performs as expected in the maintaining the CA (Central Artery) compartment pressure when simulating orientations ranging from supine to standing. The model appears to generally overpredict heart rate and thus cardiac output, possibly indicating sensitivity to the nominal heart rate, which is used as an initial set point of the regulation mechanisms. Despite this sensitivity, the model performs consistently for many hours of simulation time, indicating the success of our quasi-static implementation approach.

biomechanics↗
NASA NTRSDate not supplied

Effects of Mild Hypobaric Hypoxia on Visual Field Impairment

INTRODUCTION: The primary objective of the Exploration Atmosphere (EA) study is to validate a new prebreathe protocol necessary before exposure to a suited hypobaric environment during extravehicular activity (EVA) from a habitat ‘exploration atmosphere’ of 56.5kPa (8.2 psia), 34% O2, 66% N2. Prebreathe protocols must be time and resource efficient while also controlling Decompression Sickness (DCS) risk to within acceptable limits. The habitat hypobaric exploration atmosphere also results in a mildly hypoxic environment (piO2 = 128mmHg). As a secondary objective of the EA study, we characterized the effects of 11-day exposure to a mild hypobaric hypoxic environment on visual performance. METHODS: Two, 11-day hypobaric chamber tests were performed (EA-1and EA-2, n=8 each) in NASA’s 20-foot chamber at Johnson Space Center where subjects lived in the exploration atmosphere. Subjects also underwent simulated 6-hour EVAs at 85% O2 and 29.6 kPa during EVA on days 3, 5, 7, 9, and 11. Visual acuity (VA), a measure of spatial resolution, and contrast sensitivity (CS), a measure of ability to distinguish ever finer increments of brightness, were assessed on non-EVA days by using gapped Landolt C testing. The luminance was controlled by using a booth, a light monitor, and a lighting rheostat. EA-1 data had revealed problems in lighting control impacting consistency of the data. Procedures were subsequently updated for the EA-2 test. RESULTS: EA-1 data revealed large variance and data recording errors and was removed from the analysis. One participant left the study at Test Day 3 during EA-2. EA-2 ANOVA results showed CS (mean change=0.010 logCSWeber) and VA (mean change, -0.016 logMAR) between pre-test and 11-day test phases; however, neither VA nor CS changes were statistically significant. There were non-statistically significant declines in VA across test phases. DISCUSSION: Overall, visual field performance did not exhibit clinically significant changes (3 lines or greater change in LogMar chart) during exposure to the mild hypoxic exploration atmosphere environment compared to pre-test baseline. The consistency and stability of VA data during EA-2 suggests that the mild hypobaric hypoxic environment did not cause clinically significant negative impacts to participants’ visual field performance.

Visual Acuity↗
NASA NTRSDate not supplied

Effects of Mild Hypobaric Hypoxia on Visual Field Impairment

INTRODUCTION: The primary objective of the Exploration Atmosphere (EA) study is to validate a new prebreathe protocol necessary before exposure to a suited hypobaric environment during extravehicular activity (EVA) from a habitat ‘exploration atmosphere’ of 56.5kPa (8.2 psia), 34% O2, 66% N2. Prebreathe protocols must be time and resource efficient while also controlling Decompression Sickness (DCS) risk to within acceptable limits. The habitat hypobaric exploration atmosphere also results in a mildly hypoxic environment (piO2 = 128mmHg). As a secondary objective of the EA study, we characterized the effects of 11-day exposure to a mild hypobaric hypoxic environment on visual performance. METHODS: Two, 11-day hypobaric chamber tests were performed (EA-1and EA-2, n=8 each) in NASA’s 20-foot chamber at Johnson Space Center where subjects lived in the exploration atmosphere. Subjects also underwent simulated 6-hour EVAs at 85% O2 and 29.6 kPa during EVA on days 3, 5, 7, 9, and 11. Visual acuity (VA), a measure of spatial resolution, and contrast sensitivity (CS), a measure of ability to distinguish ever finer increments of brightness, were assessed on non-EVA days by using gapped Landolt C testing. The luminance was controlled by using a booth, a light monitor, and a lighting rheostat. EA-1 data had revealed problems in lighting control impacting consistency of the data. Procedures were subsequently updated for the EA-2 test. RESULTS: EA-1 data revealed large variance and data recording errors and was removed from the analysis. One participant left the study at Test Day 3 during EA-2. EA-2 ANOVA results showed CS (mean change=0.010 logCSWeber) and VA (mean change, -0.016 logMAR) between pre-test and 11-day test phases; however, neither VA nor CS changes were statistically significant. There were non-statistically significant declines in VA across test phases. DISCUSSION: Overall, visual field performance did not exhibit clinically significant changes (3 lines or greater change in LogMar chart) during exposure to the mild hypoxic exploration atmosphere environment compared to pre-test baseline. The consistency and stability of VA data during EA-2 suggests that the mild hypobaric hypoxic environment did not cause clinically significant negative impacts to participants’ visual field performance.

Visual Acuity↗
NASA NTRS1999

Short-latency primate vestibuloocular responses during translation

Short-lasting, transient head displacements and near target fixation were used to measure the latency and early response gain of vestibularly evoked eye movements during lateral and fore-aft translations in rhesus monkeys. The latency of the horizontal eye movements elicited during lateral motion was 11.9 +/- 5.4 ms. Viewing distance-dependent behavior was seen as early as the beginning of the response profile. For fore-aft motion, latencies were different for forward and backward displacements. Latency averaged 7.1 +/- 9.3 ms during forward motion (same for both eyes) and 12.5 +/- 6.3 ms for the adducting eye (e.g., left eye during right fixation) during backward motion. Latencies during backward motion were significantly longer for the abducting eye (18.9 +/- 9.8 ms). Initial acceleration gains of the two eyes were generally larger than unity but asymmetric. Specifically, gains were consistently larger for abducting than adducting eye movements. The large initial acceleration gains tended to compensate for the response latencies such that the early eye movement response approached, albeit consistently incompletely, that required for maintaining visual acuity during the movement. These short-latency vestibuloocular responses could complement the visually generated optic flow responses that have been shown to exhibit much longer latencies.

Non-NASA Center↗
NASA NTRS2003

Coordination of Lower Limb Joints During Locomotion: The Effects of Vestibulo-Ocular Reflex Adaptation

Controlling locomotion while maintaining a stable gaze requires precise coordination between several, interdependent full-body sensorimotor subsystems (Bloomberg and Mulavara, 2003; McDonald, et al., 1997). The overall goal of this study is to determine how this full-body gaze stabilization system responds to adaptive changes in vestibuloocular reflex (VOR) function. Locomotion involves cyclical physical interactions (impacts) with the environment. Hence, focusing on a target and maintaining visual acuity during this activity may require mechanisms to manage the energy flow, so it does not disrupt the visual and vestibular sensory information processing that stabilizes gaze. It has been shown that increasing the difficulty of a gaze task (reading numbers on a screen as opposed to simply focusing on a central dot pattern) resulted in an increase in the amount of knee flexion movement during the critical phase immediately following the heel strike event (Mulavara and Bloomberg, 2003). The increase in knee flexion during the stance phase of the gait cycle has been suggested to function as a shock absorbing mechanism associated with the rapid weight transfer from the trailing to the leading leg during walking. To understand this full-body coordination, the relative contributions of each component and the resulting effects should be assessed. In this study, we hypothesized that VOR adaptation would result in a reorganization of the lower limb joint coordination during treadmill walking in a manner to facilitate the gaze stabilization task and preserve locomotor function.

Miller, Chris↗
NASA NTRS2015

Ocular Outcomes Comparison Between 14- and 70-day Head-down Tilt Bed Rest

INTRODUCTION: Ophthalmological changes, including optic disc edema with optic nerve sheath distension, posterior globe flattening with hyperopic shift, choroidal folds and cotton wool spots have been detected in some astronauts involved in long-duration spaceflights. (sup 1) It is hypothesized that elevated intracranial pressure resulting from microgravity-induced cephalad fluid shifts may be responsible for most of these findings. Head-down tilt bed rest (HTDBR) is a ground-based microgravity analog which also produces cephalad fluid shifts. It is conceivable that prolonged HDTBR exposure may induce ocular changes similar to those experienced in microgravity. Therefore, the purpose of the present study was to compare structural and functional ocular outcomes between 14- and 70-day HDTBR in healthy human subjects. It is hypothesized that 70-d HDTBR induced ocular changes of greater magnitude as compared to 14-d HDTBR. METHODS: Two HDTBR studies were conducted at the NASA Flight Analogs Research Unit, located at The University of Texas Medical Branch at Galveston, TX. Identical NASA standard screening procedures and BR conditions (e.g., strict sleep-wake cycle, standardized diet, continuous video monitoring) were implemented in both studies. Participants spent 14 and/or 70 consecutive days in a 6deg HDT position and did not engage in exercise. Subjects received weekly ocular examinations before, during, and after HDTBR. Ocular testing included: distance and near best-corrected visual acuity (BCVA), cycloplegic refraction, intraocular pressure (IOP) measurement, color vision, red dot test, modified Amsler grid test, confrontational visual field, color fundus photography and Spectral-domain OCT scans of the macula and the optic disc. Pre/post HDTBR differences between the two studies will be evaluated for BCVA, spherical equivalent, IOP, retinal nerve fiber layer (RNFL) thickness and macular OCT parameters. RESULTS: 16 (12 males and 4 females) and 6 (5 males and 1 female) subjects participated in the 14 and 70-day HDTBR studies, respectively. One subject participated in both studies. The demographic and ophthalmological characteristics of the 14-day HDTBR study have been presented elsewhere.2 In the 70- day study, subjects age averaged 39.5 +/- 7.8 years; pre- and post-HDTBR Goldmann IOP were, on average, 15.4 and 14.6 mmHg in the right eye, and 15.3 and 14.4 mmHg in the left eye, respectively; preand post-HDTBR Spectralis OCT (Heidelberg Engineering, GmbH, Heidelberg, Germany) average RNFL thickness were 103.8 and 106 μm in the right eye, and 103 and 104.3 μm in the left eye, respectively. In both studies, color vision, red dot test, modified Amsler grid test and confrontational visual field were within normal limits at all time points; no changes were detected on stereoscopic color optic disc photography. For the above outcomes, preliminary results of the pre/post HDTBR differences between the two studies will be presented at the 2015 Human Research Program Investigators' Workshop. CONCLUSIONS: Although 14-day HDTBR did not seem to induce clinically relevant ocular changes, (sup 2) a systematic evaluation and comparison with the 70-day HDTBR study results will elucidate whether the magnitude of ocular structural and functional changes is affected by the time spent in the recumbent position. Further research will also address the effects of integrated resistance and aerobic training during HDTBR on the ocular outcomes. REFERENCES: 1. Mader TH et al. Optic disc edema, globe flattening, choroidal folds, and hyperopic shifts observed in astronauts after long-duration space flight. Ophthalmology. 2011;118(10):2058-69. 2. Taibbi G et al. Ocular outcomes evaluation in a 14-day head-down bed rest study. Aviat Space Environ Med. 2014;85(10):983-92.

Cromwell, R.L.↗
NASA NTRS1998

Pursuit Eye Movements

When viewing objects, primates use a combination of saccadic and pursuit eye movements to stabilize the retinal image of the object of regard within the high-acuity region near the fovea. Although these movements involve widespread regions of the nervous system, they mix seamlessly in normal behavior. Saccades are discrete movements that quickly direct the eyes toward a visual target, thereby translating the image of the target from an eccentric retinal location to the fovea. In contrast, pursuit is a continuous movement that slowly rotates the eyes to compensate for the motion of the visual target, minimizing the blur that can compromise visual acuity. While other mammalian species can generate smooth optokinetic eye movements - which track the motion of the entire visual surround - only primates can smoothly pursue a single small element within a complex visual scene, regardless of the motion elsewhere on the retina. This ability likely reflects the greater ability of primates to segment the visual scene, to identify individual visual objects, and to select a target of interest.

Krauzlis, Rich↗
NASA NTRSDate not supplied

An Oculometric Standard to Assess the Performance of the Ocular System for Long Duration Spaceflight

Changes in the human brain, due to spaceflight, have been a challenge to the space program since its inception; a challenge that is becoming more acute as extended International Space Station (ISS) missions become routine, a return to crewed lunar exploration is about to begin, and a multi-year crewed trip to Mars is being planned. Determining the extent to which neurophysiological adaptations may adversely impact performance in operational tasks, assessing the full-time course of these changes, and identifying/mitigating any potential long-term health consequences are crucial steps required to enable safe crew-autonomous, long-duration, deep-space missions. Vision is the predominant perceptual sense used to guide cognition and motor control in humans. Thus, it is critical for the success of any future, long-duration mission to understand how long-term exposure to microgravity and to other stressors of spaceflight and their interactions, impact visual function. This is an especially challenging task given the small and disparate samples from which we have been and will be able to collect human performance data. NASA has recently been carefully tracking spaceflight-induced ophthalmic changes, driven in large part by the fluid shifts related to microgravity. In particular, a recent study of Optical Coherence Tomography (OCT) postflight measures revealed that more than two-thirds of US crew members experience significant increases in retinal thickness after 6month or longer ISS missions. Space Associated Neuro-ocular Syndrome (SANS) also includes visual acuity decrements and other ocular structural changes that could adversely impact in-flight performance as missions become longer. However, the impact of spaceflight on the visual system is not limited to the retina. Recent comparisons of pre-and post-flight brain images have revealed structural changes throughout the brain that implicate visual, visuomotor, and visual-cognitive pathways, consistent with observed functional impacts (e.g., decreased speed/accuracy/timing of fine goal-oriented movements). Current limitations on inflight testing make it very difficult to determine when and under what conditions SANS and other disruptions of human neurological subsystems arise. Currently, one cannot anticipate the time course and extent of impairment and recovery. This study addresses this knowledge gap by creating an integrated framework of the relevant existing literature on visual and oculomotor function during spaceflight with an eye towards complementing current structural measures of visuomotor impairment with new oculometric standard measures. Using eye-movement based visual function assessment and diagnostics would provide a valuable enhancement of crew health and performance monitoring in support of deepspace exploration.

Vision↗
NASA NTRS2016

Comparison of Structural and Functional Ocular Outcomes Between 14- and 70 Day Bed Rest

Purpose: To compare structural and functional ocular outcomes in healthy human subjects undergoing 14- and/or 70-day head-down-tilt bed rest (HDTBR). We hypothesized the amount of HDTBR-induced ocular changes be affected by the HDTBR duration. Methods: The studies were conducted at the NASA Flight Analogs Research Unit, The University of Texas Medical Branch at Galveston, Galveston, TX. Participants were selected using NASA standard screening procedures. Standardized NASA screening procedures and bed rest conditions (e.g., strict sleep-wake cycle, standardized diet, continuous video monitoring) were implemented in both studies. Participants maintained a 6deg HDTBR position for 14 and/or 70 consecutive days and did not engage in exercise. Weekly ophthalmological examinations were conducted in the sitting (pre/post-bed rest only) and HDT positions. Ocular outcomes of interest included: near best-corrected visual acuity (BCVA); spherical equivalent, as determined by cycloplegic autorefraction; Goldmann applanation tonometry and iCare (Icare Finland Oy, Espoo, Finland) intraocular pressure (IOP) measurement; color vision; red dot test; modified Amsler grid test; confrontational visual field; stereoscopic color fundus photography; Spectralis OCT (Heidelberg Engineering, GmbH, Heidelberg, Germany) retinal nerve fiber layer thickness (RNFLT), peripapillary and macular retinal thicknesses. Mixed-effects linear models were used to compare pre- and post-HDTBR observations between 14- and 70-day HDTBR for our continuously scaled outcomes.

Cromwell, R. L.↗
NASA NTRS2016

Analysis by NASA's VESGEN Software of Retinal Blood Vessels Before and After 70-Day Bed Rest: A Retrospective Study

Significant risks for visual impairment associated with increased intracranial pressure (VIIP) are incurred by microgravity spaceflight, especially long-duration missions. Impairments include decreased near visual acuity, posterior globe flattening, choroidal folds, optic disc edema and cotton wool spots. We hypothesize that microgravity-induced fluid shifts result in pathological changes within the retinal blood vessels that precede development of visual and other ocular impairments. Potential contributions of retinal vascular remodeling to VIIP etiology are therefore being investigated by NASAs innovative VESsel GENeration Analysis (VESGEN) software for two studies: (1) head-down tilt in human subjects before and after 70 days of bed rest, and (2) U.S. crew members before and after ISS missions. VESGEN analysis in previous research supported by the US National Institutes of Health identified surprising new opportunities to regenerate retinal vessels during early-stage, potentially reversible progression of the visually impairing and blinding disease, diabetic retinopathy.

Vascular↗
NASA NTRS1998

Role of the flocculus of the cerebellum in motor learning of the vestibulo-ocular reflex

Structure-function studies at the systems level are an effective method for understanding the relationship of the central nervous system to behavior. Motor learning or adaptation of the vestibulo-ocular reflex is a clear example wherein this approach has been productive. During a vestibulo-ocular reflex the brain converts a head velocity signal, transduced through the vestibular semicircular canals, into an eye movement command delivered to the extraocular muscles. If the viewed target remains on the fovea of the retina, the reflex is compensatory, and its gain, eye velocity/head velocity, is one. When the image of the viewed object slips across the retina, visual acuity decreases, and the gain of the reflex, which is no longer one, is plastically adapted or adjusted until retinal stability is restored. The anatomic substrate for this plasticity thus involves brain structures in which visual-vestibular interaction can potentially occur, as well as vestibular and visual sensory and oculomotor motor structures. Further, it has been known for many years that removal of the flocculus of the cerebellum permanently precludes further vestibulo-ocular reflex adaptation, demonstrating the involvement of the cerebellum in this behavior. Maekawa and Simpson (J Neurophysiol 1973;36: 649-66) discovered that one visual input to the flocculus involved the accessory optic system and the inferior olive. Ensuing work has demonstrated that the visual signals used to adapt the vestibulo-ocular reflex are transmitted by this accessory optic system to the flocculus and subsequently to brain stem structures involved in vestibulo-ocular reflex plasticity. Presently the inclusive list of anatomic sites involved in vestibulo-ocular reflex circuitry and its adaptive plasticity is small. Our laboratory continues to believe that this behavior should be caused by interactions within this small class of neurons. By studying each class of identified neuron and its interactions with others within the list, we hope to ultimately understand the mechanisms used by the brain in the expression of this behavior.

Non-NASA Center↗
NASA NTRS2012

An Integrated Biomechanical Model for Microgravity-Induced Visual Impairment

When gravitational unloading occurs upon entry to space, astronauts experience a major shift in the distribution of their bodily fluids, with a net headward movement. Measurements have shown that intraocular pressure spikes, and there is a strong suspicion that intracranial pressure also rises. Some astronauts in both short- and long-duration spaceflight develop visual acuity changes, which may or may not reverse upon return to earth gravity. To date, of the 36 U.S. astronauts who have participated in long-duration space missions on the International Space Station, 15 crew members have developed minor to severe visual decrements and anatomical changes. These ophthalmic changes include hyperopic shift, optic nerve distension, optic disc edema, globe flattening, choroidal folds, and elevated cerebrospinal fluid pressure. In order to understand the physical mechanisms behind these phenomena, NASA is developing an integrated model that appropriately captures whole-body fluids transport through lumped-parameter models for the cerebrospinal and cardiovascular systems. This data feeds into a finite element model for the ocular globe and retrobulbar subarachnoid space through time-dependent boundary conditions. Although tissue models and finite element representations of the corneo-scleral shell, retina, choroid and optic nerve head have been integrated to study pathological conditions such as glaucoma, the retrobulbar subarachnoid space behind the eye has received much less attention. This presentation will describe the development and scientific foundation of our holistic model.

Nelson, Emily S.↗
NASA NTRS1992

Armstrong Laboratory Space Visual Function Tester Program

Viewgraphs on space visual function tester program are presented. Many astronauts and cosmonauts have commented on apparent changes in their vision while on-orbit. Comments have included descriptions of earth features and objects that would suggest enhanced distance visual acuity. In contrast, some cosmonaut observations suggest a slight loss in their object discrimination during initial space flight. Astronauts have also mentioned a decreased near vision capability that did not recover to normal until return to earth. Duntley space vision experiment, USSR space vision experiments, and visual function testers are described.

Oneal, Melvin R.↗
NASA NTRS2017

Fluid Shifts

Introduction. NASA's Human Research Program is focused on addressing health risks associated with long-duration missions on the International Space Station (ISS) and future exploration-class missions beyond low Earth orbit. Visual acuity changes observed after short-duration missions were largely transient, but now more than 50 percent of ISS astronauts have experienced more profound, chronic changes with objective structural findings such as optic disc edema, globe flattening and choroidal folds. These structural and functional changes are referred to as the visual impairment and intracranial pressure (VIIP) syndrome. Development of VIIP symptoms may be related to elevated intracranial pressure (ICP) secondary to spaceflight-induced cephalad fluid shifts, but this hypothesis has not been tested. The purpose of this study is to characterize fluid distribution and compartmentalization associated with long-duration spaceflight and to determine if a relation exists with vision changes and other elements of the VIIP syndrome. We also seek to determine whether the magnitude of fluid shifts during spaceflight, as well as any VIIP-related effects of those shifts, are predicted by the crewmember's pre-flight status and responses to acute hemodynamic manipulations, specifically posture changes and lower body negative pressure. Methods. We will examine a variety of physiologic variables in 10 long-duration ISS crewmembers using the test conditions and timeline presented in the figure below. Measures include: (1) fluid compartmentalization (total body water by D2O, extracellular fluid by NaBr, intracellular fluid by calculation, plasma volume by CO rebreathe, interstitial fluid by calculation); (2) forehead/eyelids, tibia, and calcaneus tissue thickness (by ultrasound); (3) vascular dimensions by ultrasound (jugular veins, cerebral and carotid arteries, vertebral arteries and veins, portal vein); (4) vascular dynamics by MRI (head/neck blood flow, cerebrospinal fluid pulsatility); (5) ocular measures (optical coherence tomography; intraocular pressure; 2-dimensional ultrasound including optic nerve sheath diameter, globe flattening, and retina-choroid thickness; Doppler ultrasound of ophthalmic and retinal arteries and veins); (6) cardiac variables by ultrasound (inferior vena cava, tricuspid flow and tissue Doppler, pulmonic valve, stroke volume, right heart dimensions and function, four-chamber views); and (7) ICP measures (tympanic membrane displacement, otoacoustic emissions). Pre- and post-flight, acute head-down tilt will induce cephalad fluid shifts, whereas lower body negative pressure will oppose these shifts. Controlled Mueller maneuvers will manipulate cardiovascular variables. Through interventions applied before, during, and after flight, we intend to fully evaluate the relationship between fluid shifts and the VIIP syndrome. Discussion. Ten subjects have consented to participate in this experiment, including the recent One-Year Mission crewmembers, who have recently completed R plus180 testing; all other subjects have completed pre-flight testing. Preliminary results from the One-Year Mission crewmembers will be presented, including measures of ocular structure and function, vascular dimensions, fluid distribution, and non-invasive estimates of intracranial pressure.

Stenger, M. B.↗