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Spaceflight associated neuro-ocular syndrome (SANS): an update on potential microgravity-based pathophysiology and mitigation development

Abstract

Long-duration spaceflight is associated with neurologic and ophthalmic clinical and imaging findings in astronauts termed spaceflight associated neuro-ocular syndrome (SANS). These microgravity-induced findings have been well documented by the National Aeronautics and Space Administration (NASA) and are clearly a potential risk for future human space exploration. The underlying pathogenesis of SANS is not well understood, although multiple hypotheses have emerged. Terrestrial analogues and potential countermeasures have also been studied to further understand and potentially mitigate SANS. In this manuscript, we review the current understanding of SANS, discuss the prevailing hypotheses for pathogenesis, and describe current developments in terrestrial analogues and potential countermeasures for SANS.

摘要 摘要

太空飞行相关神经视觉综合征 (Spaceflight associated neuro-ocular syndrome, SANS) 是指长时间的太空飞行与宇航员的神经和眼科临床和影像的病理性改变。美国国家航空航天局 (National Aeronautics and Space Administration, NASA) 已经详细记录了这些由微重力引起的病理性改变, 这显然是未来人类探索太空的一个潜在风险。尽管出现了多种假设, 但SANS的潜在发病机制仍不清楚。为了进一步了解和缓解SANS, 同时研究了陆地上的类似物与潜在的应对措施。本文回顾了目前对SANS的理解, 讨论了发病机制的假说, 并描述了目前陆地上的类似物与SANS的潜在对策的发展。

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Fig. 1: Pre-flight, in-flight (R-30, 30 days before returning to Earth), and post-flight (R+4, 4 days before returning to Earth) Multicolor Imaging in an astronaut that developed spaceflight associated neuro-ocular syndrome (SANS) during a spaceflight mission.

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References

  1. Demontis GC, Germani MM, Caiani EG, Barravecchia I, Passino C, Angeloni D. Human pathophysiological adaptations to the space environment. Front Physiol. 2017;8:547 https://doi.org/10.3389/fphys.2017.00547

    Article  PubMed  PubMed Central  Google Scholar 

  2. Patel ZS, Brunstetter TJ, Tarver WJ, Whitmire AM, Zwart SR, Smith SM, et al. Red risks for a journey to the red planet: the highest priority human health risks for a mission to Mars. NPJ Microgravity. 2020;6:33 https://doi.org/10.1038/s41526-020-00124-6

    Article  PubMed  PubMed Central  Google Scholar 

  3. Ong J, Lee AG. An introduction to space medicine and the physiological effects of spaceflight on the human body. In: Lee AG, Ong J, editors. Spaceflight associated neuro-ocular syndrome. Cambridge, MA: Academic Press; 2022. p. 1–7. https://doi.org/10.1016/B978-0-323-91524-3.00007-7

  4. Lee AG, Mader TH, Gibson CR, Tarver W, Rabiei P, Riascos RF, et al. Spaceflight associated neuro-ocular syndrome (SANS) and the neuro-ophthalmologic effects of microgravity: a review and an update. NPJ Microgravity. 2020;6:7 https://doi.org/10.1038/s41526-020-0097-9

    Article  PubMed  PubMed Central  Google Scholar 

  5. Lee AG, Mader TH, Gibson CR, Brunstetter TJ, Tarver WJ. Space flight-associated neuro-ocular syndrome (SANS). Eye. 2018;32:1164–7. https://doi.org/10.1038/s41433-018-0070-y

    Article  PubMed  PubMed Central  Google Scholar 

  6. Mader TH, Gibson CR, Pass AF, Kramer LA, Lee AG, Fogarty J, et al. Optic disc edema, globe flattening, choroidal folds, and hyperopic shifts observed in astronauts after long-duration space flight. Ophthalmology. 2011;118:2058–69. https://doi.org/10.1016/j.ophtha.2011.06.021

    Article  PubMed  Google Scholar 

  7. Ong J, Tavakkoli A, Strangman G, Zaman N, Kamran SA, Zhang Q. et al. Neuro-ophthalmic imaging and visual assessment technology for spaceflight associated neuro-ocular syndrome (SANS). Surv Ophthalmol. 2022;67:1443–66. https://doi.org/10.1016/j.survophthal.2022.04.004

    Article  PubMed  Google Scholar 

  8. Mader TH, Gibson CR, Otto CA, Sargsyan AE, Miller NR, Subramanian PS, et al. Persistent asymmetric optic disc swelling after long-duration space flight: implications for pathogenesis. J Neuroophthalmol. 2017;37:133–9. https://doi.org/10.1097/WNO.0000000000000467

    Article  PubMed  Google Scholar 

  9. Mader TH, Gibson CR, Barratt MR, Miller NR, Subramanian PS, Killer HE, et al. Persistent globe flattening in astronauts following long-duration spaceflight. Neuroophthalmology. 2021;45:29–35. https://doi.org/10.1080/01658107.2020.1791189

    Article  PubMed  Google Scholar 

  10. Mader TH, Gibson CR, Pass AF, Lee AG, Killer HE, Hansen HC, et al. Optic disc edema in an astronaut after repeat long-duration space flight. J Neuroophthalmol. 2013;33:249–55. https://doi.org/10.1097/WNO.0b013e31829b41a6

    Article  PubMed  Google Scholar 

  11. Wall M. Idiopathic intracranial hypertension. Neurol Clin. 2010;28:593–617. https://doi.org/10.1016/j.ncl.2010.03.003

    Article  PubMed  PubMed Central  Google Scholar 

  12. Lawley JS, Petersen LG, Howden EJ, Sarma S, Cornwell WK, Zhang R, et al. Effect of gravity and microgravity on intracranial pressure. J Physiol. 2017;595:2115–27. https://doi.org/10.1113/JP273557

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Berdahl JP, Yu DY, Morgan WH. The translaminar pressure gradient in sustained zero gravity, idiopathic intracranial hypertension, and glaucoma. Med Hypotheses. 2012;79:719–24. https://doi.org/10.1016/j.mehy.2012.08.009

    Article  PubMed  Google Scholar 

  14. Zhang LF, Hargens AR. Spaceflight-induced intracranial hypertension and visual impairment: pathophysiology and countermeasures. Physiol Rev. 2018;98:59–87. https://doi.org/10.1152/physrev.00017.2016

    Article  PubMed  Google Scholar 

  15. Benveniste H, Liu X, Koundal S, Sanggaard S, Lee H, Wardlaw J. The glymphatic system and waste clearance with brain aging: a review. Gerontology. 2019;65:106–19. https://doi.org/10.1159/000490349

    Article  PubMed  Google Scholar 

  16. Kasi A, Liu C, Faiq MA, Chan KC. Glymphatic imaging and modulation of the optic nerve. Neural Regen Res. 2022;17:937–47. https://doi.org/10.4103/1673-5374.324829

    Article  CAS  PubMed  Google Scholar 

  17. Wostyn P, De Deyn PP. The “Ocular Glymphatic System”: an important missing piece in the puzzle of optic disc edema in astronauts? Invest Ophthalmol Vis Sci. 2018;59:2090–1. https://doi.org/10.1167/iovs.17-23263

    Article  PubMed  Google Scholar 

  18. Wostyn P, Mader TH, Gibson CR, Killer HE. The perivascular space of the central retinal artery as a potential major cerebrospinal fluid inflow route: implications for optic disc edema in astronauts. Eye. 2020;34:779–80. https://doi.org/10.1038/s41433-019-0594-9

    Article  PubMed  Google Scholar 

  19. Wostyn P, Mader TH, Gibson CR, Killer HE. The escape of retrobulbar cerebrospinal fluid in the astronaut’s eye: mission impossible? Eye. 2019;33:1519–24. https://doi.org/10.1038/s41433-019-0453-8

    Article  PubMed  PubMed Central  Google Scholar 

  20. Mader TH, Taylor GR, Hunter N, Caputo M, Meehan RT. Intraocular pressure, retinal vascular, and visual acuity changes during 48 h of 10 degrees head-down tilt. Aviat Space Environ Med. 1990;61:810–3

    CAS  PubMed  Google Scholar 

  21. Mader TH, Gibson CR, Caputo M, Hunter N, Taylor G, Charles J, et al. Intraocular pressure and retinal vascular changes during transient exposure to microgravity. Am J Ophthalmol. 1993;115:347–50. https://doi.org/10.1016/s0002-9394(14)73586-x

    Article  CAS  PubMed  Google Scholar 

  22. Draeger J, Schwartz R, Groenhoff S, Stern C. Self-tonometry under microgravity conditions. Clin Investig. 1993;71:700–3. https://doi.org/10.1007/BF00209723

    Article  CAS  PubMed  Google Scholar 

  23. Macias BR, Patel NB, Gibson CR, Samuels BC, Laurie SS, Otto C, et al. Association of long-duration spaceflight with anterior and posterior ocular structure changes in astronauts and their recovery. JAMA Ophthalmol. 2020;138:553–9. https://doi.org/10.1001/jamaophthalmol.2020.0673

    Article  PubMed  Google Scholar 

  24. Feola AJ, Nelson ES, Myers J, Ethier CR, Samuels BC. The impact of choroidal swelling on optic nerve head deformation. Invest Ophthalmol Vis Sci. 2018;59:4172–81. https://doi.org/10.1167/iovs.18-24463

    Article  PubMed  Google Scholar 

  25. Wostyn P, Gibson CR, Mader TH. Optic disc edema in astronauts from a choroidal point of view. Aerosp Med Hum Perform. 2022;93:396–8. https://doi.org/10.3357/AMHP.6010.2022

    Article  PubMed  Google Scholar 

  26. Taniguchi-Shinojima A. Mechanical alterations of the brain and optic chiasm in Spaceflight Associated Neuro-Ocular Syndrome. In: Lee AG, Ong J, editors. Spaceflight associated neuro-ocular syndrome. Cambridge, MA: Academic Press; 2022. p. 77–84. https://doi.org/10.1016/B978-0-323-91524-3.00014-4

  27. Roberts DR, Albrecht MH, Collins HR, Asemani D, Chatterjee AR, Spampinato MV, et al. Effects of spaceflight on astronaut brain structure as indicated on MRI. N Engl J Med. 2017;377:1746–53. https://doi.org/10.1056/NEJMoa1705129

    Article  PubMed  Google Scholar 

  28. Shinojima A, Kakeya I, Tada S. Association of space flight with problems of the brain and eyes. JAMA Ophthalmol. 2018;136:1075–6. https://doi.org/10.1001/jamaophthalmol.2018.2635

    Article  PubMed  PubMed Central  Google Scholar 

  29. Strangman GE, Zhang Q, Marshall-Goebel K, Mulder E, Stevens B, Clark JB, et al. Increased cerebral blood volume pulsatility during head-down tilt with elevated carbon dioxide: the SPACECOT Study. J Appl Physiol (1985). 2017;123:62–70. https://doi.org/10.1152/japplphysiol.00947.2016

    Article  CAS  PubMed  Google Scholar 

  30. Galdamez LA, Brunstetter TJ, Lee AG, Tarver WJ. Origins of cerebral edema: implications for spaceflight-associated neuro-ocular syndrome. J Neuroophthalmol. 2020;40:84–91. https://doi.org/10.1097/WNO.0000000000000852

    Article  PubMed  Google Scholar 

  31. Galdamez L. Pathophysiology of cerebral edema and its connection to Spaceflight Associated Neuro-Ocular Syndrome. In: Lee AG, Ong J, editors. Spaceflight associated neuro-ocular syndrome. Cambridge, MA: Academic Press; 2022. p. 107–33 https://doi.org/10.1016/B978-0-323-91524-3.00002-8

  32. Zheng H, Chen C, Zhang J, Hu Z. Mechanism and therapy of brain edema after intracerebral hemorrhage. Cerebrovasc Dis. 2016;42:155–69. https://doi.org/10.1159/000445170

    Article  PubMed  Google Scholar 

  33. Candelario-Jalil E, Yang Y, Rosenberg GA. Diverse roles of matrix metalloproteinases and tissue inhibitors of metalloproteinases in neuroinflammation and cerebral ischemia. Neuroscience. 2009;158:983–94. https://doi.org/10.1016/j.neuroscience.2008.06.025

    Article  CAS  PubMed  Google Scholar 

  34. Zwart S, Smith S. Genetics, vitamins, and spaceflight associated neuro-ocular syndrome. In: Lee, AG, Ong, J (Ed.). Spaceflight associated neuro-ocular syndrome. 2022. https://doi.org/10.1016/B978-0-323-91524-3.00017-X

  35. Zwart SR, Gregory JF, Zeisel SH, Gibson CR, Mader TH, Kinchen JM, et al. Genotype, B-vitamin status, and androgens affect spaceflight-induced ophthalmic changes. FASEB J. 2016;30:141–8. https://doi.org/10.1096/fj.15-278457

    Article  CAS  PubMed  Google Scholar 

  36. Zwart SR, Laurie SS, Chen JJ, Macias BR, Lee S, Stenger M, et al. Association of genetics and B vitamin status with the magnitude of optic disc edema during 30-day strict head-down tilt bed rest. JAMA Ophthalmol. 2019;137:1195–1200. https://doi.org/10.1001/jamaophthalmol.2019.3124

    Article  PubMed  PubMed Central  Google Scholar 

  37. Zwart SR, Gibson CR, Mader TH, Ericson K, Ploutz-Snyder R, Heer M, et al. Vision changes after spaceflight are related to alterations in folate- and vitamin B-12-dependent one-carbon metabolism. J Nutr. 2012;142:427–31. https://doi.org/10.3945/jn.111.154245

    Article  CAS  PubMed  Google Scholar 

  38. Ong J, Tarver W, Brunstetter T, Mader T, Gibson CR, Mason SS, et al. Spaceflight associated neuro-ocular syndrome: proposed pathogenesis, terrestrial analogues, and emerging countermeasures. Br J Ophthalmol. 2023. https://doi.org/10.1136/bjo-2022-322892

  39. Pandiarajan M, Hargens AR. Ground-based analogs for human spaceflight. Front Physiol. 2020;11:716 https://doi.org/10.3389/fphys.2020.00716

    Article  PubMed  PubMed Central  Google Scholar 

  40. Shelhamer M. Parabolic flight as a spaceflight analog. J Appl Physiol (1985). 2016;120:1442–8. https://doi.org/10.1152/japplphysiol.01046.2015

    Article  PubMed  Google Scholar 

  41. Ong J, Lee AG, Moss HE. Head-down tilt bed rest studies as a terrestrial analog for spaceflight associated neuro-ocular syndrome. Front Neurol. 2021;12:648958 https://doi.org/10.3389/fneur.2021.648958

    Article  PubMed  PubMed Central  Google Scholar 

  42. Laurie SS, Macias BR, Dunn JT, Young M, Stern C, Lee S, et al. Optic disc edema after 30 days of strict head-down tilt bed rest. Ophthalmology. 2019;126:467–8. https://doi.org/10.1016/j.ophtha.2018.09.042

    Article  PubMed  Google Scholar 

  43. Laurie SS, Greenwald SH, Marshall-Goebel K, Pardon LP, Gupta A, Lee S, et al. Optic disc edema and chorioretinal folds develop during strict 6 degrees head-down tilt bed rest with or without artificial gravity. Physiol Rep. 2021;9:e14977 https://doi.org/10.14814/phy2.14977

    Article  PubMed  PubMed Central  Google Scholar 

  44. Taibbi G, Young M, Vyas RJ, Murray MC, Lim S, Predovic M, et al. Opposite response of blood vessels in the retina to 6 degrees head-down tilt and long-duration microgravity. NPJ Microgravity. 2021;7:38 https://doi.org/10.1038/s41526-021-00165-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Vyas RJ, Young M, Murray MC, Predovic M, Lim S, Jacobs NM, et al. Decreased vascular patterning in the retinas of astronaut crew members as new measure of ocular damage in spaceflight-associated neuro-ocular syndrome. Investig Ophthalmol Vis Sci. 2020;61:34 https://doi.org/10.1167/iovs.61.14.34

    Article  Google Scholar 

  46. Laurie SS, Lee S, Macias BR, Patel N, Stern C, Young M, et al. Optic disc edema and choroidal engorgement in astronauts during spaceflight and individuals exposed to bed rest. JAMA Ophthalmol. 2020;138:165–72. https://doi.org/10.1001/jamaophthalmol.2019.5261

    Article  PubMed  Google Scholar 

  47. Crystal GJ, Salem MR. Lower body negative pressure: historical perspective, research findings, and clinical applications. J Anesth Hist. 2015;1:49–54. https://doi.org/10.1016/j.janh.2015.02.005

    Article  PubMed  Google Scholar 

  48. Scott JM, Tucker WJ, Martin D, Crowell JB, Goetchius E, Ozgur O, et al. Association of exercise and swimming goggles with modulation of cerebro-ocular hemodynamics and pressures in a model of spaceflight-associated neuro-ocular syndrome. JAMA Ophthalmol. 2019;137:652–9. https://doi.org/10.1001/jamaophthalmol.2019.0459

    Article  PubMed  PubMed Central  Google Scholar 

  49. Robin A, Auvinet A, Degryse B, Murphy R, Bareille MP, Beck A, et al. DI-5-CUFFS: venoconstrictive thigh cuffs limit body fluid changes but not orthostatic intolerance induced by a 5-day dry immersion. Front Physiol. 2020;11:383 https://doi.org/10.3389/fphys.2020.00383

    Article  PubMed  PubMed Central  Google Scholar 

  50. Ashari N, Hargens AR. The mobile lower body negative pressure gravity suit for long-duration spaceflight. Front Physiol. 2020;11:977 https://doi.org/10.3389/fphys.2020.00977

    Article  PubMed  PubMed Central  Google Scholar 

  51. Petersen LG, Hargens A, Bird EM, Ashari N, Saalfeld J, Petersen J. Mobile lower body negative pressure suit as an integrative countermeasure for spaceflight. Aerosp Med Hum Perform. 2019;90:993–9. https://doi.org/10.3357/AMHP.5408.2019

    Article  PubMed  Google Scholar 

  52. Anderson AP, Butterfield JS, Subramanian PS, Clark TK. Intraocular pressure and cardiovascular alterations investigated in artificial gravity as a countermeasure to spaceflight associated neuro-ocular syndrome. J Appl Physiol (1985). 2018;125:567–76. https://doi.org/10.1152/japplphysiol.00082.2018

    Article  PubMed  Google Scholar 

  53. Goswami N, Blaber AP, Hinghofer-Szalkay H, Convertino VA. Lower body negative pressure: physiological effects, applications, and implementation. Physiol Rev. 2019;99:807–51. https://doi.org/10.1152/physrev.00006.2018

    Article  CAS  PubMed  Google Scholar 

  54. Hearon CM,Jr, Dias KA, Babu G, Marshall J, Leidner J, Peters K. et al. Effect of nightly lower body negative pressure on choroid engorgement in a model of spaceflight-associated neuro-ocular syndrome: a randomized crossover trial. JAMA Ophthalmol. 2022;140:59–65. https://doi.org/10.1001/jamaophthalmol.2021.5200

    Article  PubMed  Google Scholar 

  55. Petersen LG, Lawley JS, Lilja-Cyron A, Petersen J, Howden EJ, Sarma S, et al. Lower body negative pressure to safely reduce intracranial pressure. J Physiol. 2019;597:237–48. https://doi.org/10.1113/JP276557

    Article  CAS  PubMed  Google Scholar 

  56. Pardon LP, Macias BR, Ferguson CR, Greenwald SH, Ploutz-Snyder R, Alferova IV, et al. Changes in optic nerve head and retinal morphology during spaceflight and acute fluid shift reversal. JAMA Ophthalmol. 2022;140:763–70. https://doi.org/10.1001/jamaophthalmol.2022.1946

    Article  PubMed  PubMed Central  Google Scholar 

  57. Kermorgant M, Sadegh A, Geeraerts T, Varenne F, Liberto J, Roubelat FP, et al. Effects of venoconstrictive thigh cuffs on dry immersion-induced ophthalmological changes. Front Physiol. 2021;12:692361 https://doi.org/10.3389/fphys.2021.692361

    Article  PubMed  PubMed Central  Google Scholar 

  58. Hansen AB, Lawley JS, Rickards CA, Howden EJ, Sarma S, Cornwell WK, et al. Reducing intracranial pressure by reducing central venous pressure: assessment of potential countermeasures to spaceflight-associated neuro-ocular syndrome. J Appl Physiol (1985). 2021;130:283–9. https://doi.org/10.1152/japplphysiol.00786.2020

    Article  CAS  PubMed  Google Scholar 

  59. NASA. Equinox balance goggles: the effects of local orbital pressure changes on intraocular pressure (NCC958SMST00012). NASA life sciences data archive. 2015. https://taskbook.nasaprs.com/tbp/index.cfm?action=public_query_taskbook_content&TASKID=10645. Accessed March 1, 2023

  60. Smith SM, Zwart SR. Spaceflight-related ocular changes: the potential role of genetics, and the potential of B vitamins as a countermeasure. Curr Opin Clin Nutr Metab Care. 2018;21:481–8. https://doi.org/10.1097/MCO.0000000000000510

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Tyson Brunstetter, OD, PhD and William Tarver, MD, MPH for their review and input for this manuscript.

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JO drafted the initial manuscript. THM, CRG, SSM, and AGL provided critical edits and feedback for the manuscript. All authors contributed to the final version of the manuscript.

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Ong, J., Mader, T.H., Gibson, C.R. et al. Spaceflight associated neuro-ocular syndrome (SANS): an update on potential microgravity-based pathophysiology and mitigation development. Eye 37, 2409–2415 (2023). https://doi.org/10.1038/s41433-023-02522-y

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