Factors Accompanying Spaceflights:effects on the retina: History
View Latest Version
Please note this is an old version of this entry, which may differ significantly from the current revision.
Contributor:
Eleonora N. Grigoryan

Spaceflight (SF) increases the risk of developmental, regenerative, and physiological disorders in animals and humans. Astronauts, besides bone loss, muscle atrophy, and cardiovascular and immune system alterations, undergo ocular disorders affecting posterior eye tissues, including the retina. Under microgravity conditions, mammals show disturbances in the retinal vascular system and increased risk of oxidative stress that can lead to cell death in the retina.

  • vertebrates
  • human
  • eye
  • retina
  • spaceflight
  • microgravity
  • hyper-gravity
  • irradiation

1. Introduction

Outer space is an environment alien to both humans and other vertebrates living on Earth. Such factors as microgravity (μg) and cosmic radiation make being in space dangerous. Long-term orbital flights often cause organic and systemic changes in the body, although they also trigger mechanisms of physiological adaptation to the extraordinary conditions of spaceflights (SF). Effects of μg on the redistribution of fluids, including blood, in the body are known. The cardiovascular system counteracts gravity when it pumps blood to the upper body, but it also uses the pull of gravity when it distributes fluid to the lower extremities. The conditions of μg alter the functions of the cardiovascular system and eye blood supply [1][2][3]. SF is known to have a negative effect on the central nervous system [4][5][6][7]. Moreover, muscle and bone mass loss, anemia, and immune system suppression were also documented [8][9][10].
Despite the protection created in spacecrafts, cosmic radiation, as a co-factor of SF, and μg exert a combined negative effect [11]. The eye and the retina, being one of the most sensitive systems of perception of the environment, are exposed to both [12]. Astronauts (cosmonauts, or taikonauts) during SF suffer a reduction and changes in vision, which are collectively referred to as spaceflight-associated neuro-ocular syndrome (SANS) [13][14].
In recent decades, numerous μg-associated pathological and physiological changes have been investigated at different levels of vertebrate organization, from single cells to a whole adult organism. However, only a small portion of studies have considered the effect of altered gravity on the visual system, the development and regeneration of eye tissues, and, in particular, the retina of animals in vivo. Beyond the sufficiently close investigation and elucidation of SANS in the literature, when analyzing available information, researchers find only scattered data obtained on different models of vertebrates in vivo, from fish to mammals. There is only scarce evidence about the behavior of retinal cells and the expression of genes and proteins in them when cultured in vitro under μg conditions. In many cases, these are results of laboratory in vivo and in vitro experiments simulating weightlessness close to physiological, the so-called simulated microgravity (s-μg). The range of issues to address using a vertebrate retina model in vivo under μg conditions is still also narrow. A few studies consider the retina development in fish and birds, the retina regeneration in amphibians, and changes in the retina of adult mammals, mainly small rodents. Data on the molecular mechanisms that provide the development patterns, regeneration/recovery of the retina, and its structural changes in SF conditions are even scarcer. There is also a very small range of studies that take into account the radiation effects in cases of μg exposure and on animals exposed to hyper-gravity (hg). Although the amount of information accumulated over more than half a century is not as sufficient, often scattered and fragmentary, it provides basic views of the effect that low gravity doses have on eye tissues: retina (both, neural portion of the retina and RPE), optic nerve (ON), choroid, lens, and cornea of human and other vertebrates. Currently, experiments using rodents are a priority, since the results of such approaches can potentially be transferred to a human eye model in order to prevent or address some vision problems faced by astronauts in SFs. However, all, without exception, studies using in vivo animal models conducted aboard a spacecraft are relevant for the development of fundamental aspects of the visual system biology in various animals exposed to SF conditions. Understanding the emergence and progress of changes, the potential and the pattern of adaptation, regeneration, and restoration of eye tissues, molecular mechanisms regulating these processes, etc. is of high importance. The already available information in these areas requires elucidation and generalization attempts to formulate the prospects and objectives of future studies.

2. Major Factors That Influence a Living Organism Exposed to SF Conditions

The major factors that influence a living organism exposed to SF conditions are μg and ionizing cosmic radiation. Additional factors include hg experienced during takeoff and landing, magnetic field changes, an increase in CO2 concentration, circadian rhythm disturbance, vibration, behavioral and social constraints, etc., but the former two are the most influential (Figure 1).
Life 13 01263 g001 550
Figure 1. Spaceflight factors and their effects on vertebrates including humans. Microgravity and cosmic ionizing radiation are the major factors.
Microgravity (μg) is a small dose of gravity at which the force of normal (1 g) gravity acts to only a low extent, and the body experiences weightlessness. SF conditions do not mean the complete lack of the gravity effect, but its dose is significantly reduced to values between 0.0001 and 0.000001× g (on average, 10−6) [15]. Over the years of research on board spacecrafts and after SF, as well as in experiments using s-μg, the adverse effect of long-term μg exposure on many systems of the body has become evident. Changes affect the visual, central nervous, musculoskeletal, cardiovascular, and immune systems as well as cell responses and the expression of many genes. Information collected on in vivo animal models, on humans, and isolated cells and tissues in vitro under s-μg and r-μg conditions has been summarized in numerous reviews elsewhere (see, for example, [9][16][17][18][19]). The data concerning the pattern of influence of r-μg and s-μg on the structures of the eye in general and the retina in particular are provided in the sections of the present review below.
Initially, it was assumed that cosmic radiation should have an effect on any living organism, including humans. This effect results from the loss of the shield created by the Earth’s atmosphere and magnetic field. In long-term SFs, the human or animal body is known to be continuously exposed to low doses of cosmic radiation including heavy ions (the so-called HZE particles) [20][21][22]. A study of the biological effect of space radiation on the mammalian body simulated in the laboratory has shown that it poses a higher cancer risk and negatively affects the functions of the cardiovascular, central nervous, and immune systems [23][24][25][26]. In vertebrates, including humans, the retina is very sensitive and subject to oxidative damage caused by the constant light radiation on Earth [27]. However, oxidative damage is an additional risk in SFs during exposure to cosmic radiation [28][29].
The variation in the effect of cosmic radiation in the conditions of μg exposure and the possible synergistic effect of the two factors are widely discussed [30][31][32][33]. Differences of the effect of space radiation on living organisms in SF compared to this effect at 1 g on Earth are documented from time to time, with information on this issue, however, being scarce, and the results still contradictory and ambiguous. This is explained by the greater attention to the role of μg and the fact that most studies are conducted without taking into account the cosmic radiation effect. Recently, researchers [11][33][34] have paid special attention to oxidative DNA damage and variations in signal transduction that occur during exposure to cosmic radiation, taking into account not only chromosomal DNA but also mitochondria. The study by Yatagai and Ishioka [31] proposes a solution for detecting the interactive effect of μg and space radiation using a broad analysis of gene expression. There is currently evidence that the combined effect of the two most important SF factors is exerted at the molecular level of cell responses: damaging and signaling by ROS, damage responses on DNA (repair, replication, transcription, etc.), and expression of gene and protein (regulation by chromatin, epigenetic control, etc.) [34]. However, it is obvious that this research approach requires modern methods of molecular biology to be introduced in the practice of experiments in SF conditions and/or when simulating the latter in a laboratory. The objective becomes even more complicated when using not only cell systems in vitro but also analyzing the molecular genetics of cell responses under the combined effect of radiation and μg on animal models in vivo.
The number of studies considering the effect of hyper-gravity (hg) on in vitro and in vivo models is not as substantial compared to that of studies on μg and cosmic ionizing radiation. On the other hand, astronauts experience, although for a short time, significant overloads during takeoff and re-entry. The effect of hg conditions is studied using short-arm human centrifugation as a possible countermeasure to treat not only spaceflight deconditioning but also provide a therapeutic approach to several pathologies [35]. During the experiment, many animal models have been studied, from insects to mammals including humans [36]. Nearly all body systems investigated are influenced by hg. Substantial anomalies have been observed in the cardiovascular, immune, vestibular, and musculoskeletal systems [37]. Thus, studies of the hg effect on changes in the mammalian musculoskeletal system show the occurrence of muscle hypertrophy, increased myogenesis, and inhibition of muscle degradation in vivo [38]. A similar effect on bone tissue has been recorded: elevation of bone mass due to the upregulation of bone formation [38]. The molecular mechanisms of the phenomenon have not yet been reported, but it is obvious that changes occur due to the regulation of genes responsible for these processes. In some of the studies, the hg effect on other tissues has been recorded: high doses of gravity can induce the synthesis of nitric oxide synthase (iNOS) in mouse kidneys [39] and disrupt the intestinal microbiota in mice [40]. A positive effect toward glial cells has been shown. Hyper-gravity promotes astrocyte reactivity aimed at suppressing axon dystrophy and stimulating neuronal regeneration [41]. Among numerous studies carried out to date using high gravity doses, no evidence of this effect on the visual system and eye tissues of vertebrates has been found except for the results of the below-described experiments using a centrifuge and newts as the animal model. Furthermore, there are large differences between the duration and values of hg created in laboratory-based experiments (days and weeks) and in SF (minutes). The body size should also be taken into account. As is assumed, the larger the body, the greater becomes its response to the impact [42]. For this reason, the data obtained in model experiments cannot be extrapolated to humans under conditions of overload during takeoff, subsequent SF, and re-entry to Earth.

This entry is adapted from the peer-reviewed paper 10.3390/life13061263

References

  1. Makarov, I.A.; Voronkov, Y.I.; Aslanjan, M.G. Ophthalmic Changes Associated with Long-Term Exposure to Microgravity. Hum. Physiol. 2017, 43, 111–120.
  2. Shen, M.; Frishman, W.H. Effects of Spaceflight on Cardiovascular Physiology and Health. Cardiol. Rev. 2019, 27, 122–126.
  3. Rohr, J.J.; Sater, S.; Sass, A.M.; Marshall-Goebel, K.; Ploutz-Snyder, R.J.; Ethier, C.R.; Stenger, M.B.; Martin, B.A.; Macias, B.R. Quantitative magnetic resonance image assessment of the optic nerve and surrounding sheath after spaceflight. NPJ Microgravity 2020, 6, 30.
  4. Vazquez, M.E. Neurobiological problems in long-term deep space flights. Adv. Space Res. 1998, 22, 171–183.
  5. Roberts, D.R.; Albrecht, M.H.; Collins, H.R.; Asemani, D.; Chatterjee, A.R.; Spampinato, M.V.; Zhu, X.; Chimowitz, M.I.; Antonucci, M.U. Effects of spaceflight on astronaut brain structure as indicated on MIR. N. Engl. J. Med. 2017, 377, 1746–1753.
  6. Rahul, J.; Hoshide, R.; Waters, J.D.; Limoli, C.L. Space–brain: The negative effects of space exposure on the central nervous system. Surg. Neurol. Int. 2018, 9, 9.
  7. Marfia, G.; Navone, S.E.; Guarnaccia, L.; Campanella, R.; Locatelli, M.; Miozzo, M.; Perelli, P.; Della Morte, G.; Catamo, L.; Tondo, P.; et al. Space flight and central nervous system: Friends or enemies? Challenges and opportunities for neuroscience and neuro-oncology. J. Neurosci. Res. 2022, 100, 1649–1663.
  8. Droppert, P.M. The effects of microgravity on the skeletal system—A review. J. Br. Interplanet. Soc. 1990, 43, 19–24.
  9. White, R.J.; Averner, M. Humans in space. Nature 2001, 409, 1115–1118.
  10. Hariom, S.K.; Ravi, A.; Mohan, J.R.; Pochiraju, H.D.; Chattopadhyay, S.; Nelson, E.J.R. Animal physiology across the gravity continuum. Acta Astronaut. 2021, 178, 522–535.
  11. Willey, J.S.; Britten, R.A.; Blaber, E.; Tahimic, C.G.T.; Chancellor, J.; Mortreux, M.; Sanford, L.D.; Kubik, A.J.; Delp, M.D.; Mao, X.W. The individual and combined effects of spaceflight radiation and microgravity on biologic systems and functional outcomes. J. Environ. Sci. Health C Toxicol. Carcinog. 2021, 39, 129–179.
  12. Taylor, H.R.; West, S.; Munoz, B.; Rosenthal, F.S.; Bressler, S.B.; Bressler, N.M. The long-term effects of visible light on the eye. Arch. Ophthalmol. 1992, 110, 99–104.
  13. Paez, Y.M.; Mudie, L.I.; Subramanian, P.S. Spaceflight associated neuro-ocular syndrome (sans): A systematic review and future directions. Eye Brain 2020, 12, 105–117.
  14. Khossravi, E.A.; Hargens, A.R. Visual disturbances during prolonged space missions. Curr. Opin. Ophthalmol. 2021, 32, 69–73.
  15. Unsworth, B.R.; Lelkes, P.I. Growing tissues in microgravity. Nat. Med. 1998, 4, 901–907.
  16. Blaber, E.; Marçal, H.; Burns, B.P. Bioastronautics: The influence of microgravity on astronaut health. Astrobiology 2010, 10, 463–473.
  17. Strauch, S.M.; Grimm, D.; Corydon, T.J.; Krüger, M.; Bauer, J.; Lebert, M.; Wise, P.; Infanger, M.; Richter, P. Current Knowledge about the Impact of Microgravity on the Proteome. Expert Rev. Proteom. 2018, 16, 5–16.
  18. Prasad, B.; Grimm, D.; Strauch, S.M.; Erzinger, G.S.; Corydon, T.J.; Lebert, M.; Magnusson, N.E.; Infanger, M.; Richter, P.; Krüger, M. Influence of Microgravity on Apoptosis in Cells, Tissues, and Other Systems In Vivo and In Vitro. Biological effects of space radiation. Int. J. Mol. Sci. 2020, 21, 9373.
  19. Grimm, D.; Wehland, M.; Corydon, T.J.; Richter, P.; Prasad, B.; Bauer, J.; Egli, M.; Kopp, S.; Lebert, M.; Krüger, M. The effects of microgravity on differentiation and cell growth in stem cells and cancer stem cells. Stem. Cells Transl. Med. 2020, 9, 882–894.
  20. Pinsky, L.S.; Osborne, W.Z.; Hoffman, R.A.; Bailey, J.V. Light flashes observed by astronauts on Skylab 4. Science 1975, 188, 928–930.
  21. Ohnishi, T.; Takahashi, A.; Ohnishi, K. Biological effects of space radiation. Biol. Sci. Space 2001, 15, S203–S210.
  22. Casolino, M.; Bidoli, V.; Morselli, A.; Narici, L.; De Pascale, M.P.; Picozza, P.; Reali, E.; Sparvoli, R.; Mazzenga, G.; Ricci, M.; et al. Space travel: Dual origins of light flashes seen in space. Nature 2003, 422, 680.
  23. Yan, X.; Sasi, S.P.; Gee, H.; Lee, J.; Yang, Y.; Mehrzad, R.; Onufrak, J.; Song, J.; Enderling, H.; Agarwal, A.; et al. Cardiovascular risks associated with low dose ionizing particle radiation. PLoS ONE 2014, 9, e110269.
  24. Rabin, B.M.; Poulose, S.M.; Carrihill-Knoll, K.L.; Ramirez, F.; Bielinski, D.F.; Heroux, N.; Shukitt-Hale, B. Acute effects of exposure to (56) Fe and (16) O particles on learning and memory. Radiat. Res. 2015, 184, 143–150.
  25. Furukawa, S.; Nagamatsu, A.; Nenoi, M.; Fujimori, A.; Kakinuma, S.; Katsube, T.; Wang, B.; Tsuruoka, C.; Shirai, T.; Nakamura, A.J.; et al. Space radiation biology for “Living in Space”. BioMed Res. Int. 2020, 2020, 4703286.
  26. Kennedy, E.M.; Powell, D.R.; Li, Z.; Bell, J.S.K.; Barwick, B.G.; Feng, H.; McCrary, M.R.; Dwivedi, B.; Kowalski, J.; Dynan, W.S.; et al. Galactic cosmic radiation induces persistent epigenome alterations relevant to human lung cancer. Sci. Rep. 2018, 8, 6709.
  27. Cingolani, C.; Rogers, B.; Lu, L.; Kachi, S.; Shen, J.; Campochiaro, P.A. Retinal degeneration from oxidative damage. Free Radic. Biol. Med. 2006, 40, 660–669.
  28. Mao, X.W.; Green, L.M.; Mekonnen, T.; Lindsey, N.; Gridley, D.S. Gene expression analysis of oxidative stress and apoptosis in proton-irradiated rat retina. In Vivo 2010, 24, 425–430.
  29. Mao, X.W.; Pecaut, M.J.; Stodieck, L.S.; Ferguson, V.L.; Bateman, T.A.; Bouxsein, M.; Jones, T.A.; Moldovan, M.; Cunningham, C.E.; Chieu, J.; et al. Spaceflight environment induces mitochondrial oxidative damage in ocular tissue. Radiat. Res. 2013, 180, 340–350.
  30. Manti, L. Does reduced gravity alter cellular response to ionizing radiation? Radiat. Environ. Biophys. 2006, 45, 1–8.
  31. Yatagai, F.; Ishioka, N. Are biological effects of space radiation really altered under the microgravity environment? Life Sci. Space Res. 2014, 3, 76–89.
  32. Moreno-Villanueva, M.; Wong, M.; Lu, T.; Zhang, Y.; Wu, H. Interplay of space radiation and microgravity in DNA damage and DNA damage response. NPJ Microgravity 2017, 3, 14.
  33. Yamanouchi, S.; Rhone, J.; Mao, J.-H.; Fujiwara, K.; Saganti, P.B.; Takahashi, A.; Hada, M. Simultaneous exposure of cultured human lymphoblastic cells to simulated microgravity and radiation increases chromosome aberrations. Life 2020, 10, 187.
  34. Yatagai, F.; Honma, M.; Dohmae, N.; Ishioka, N. Biological effects of space environmental factors: A possible interaction between space radiation and microgravity. Life Sci. Space Res. 2019, 20, 113–123.
  35. Isasi, E.; Isasi, M.E.; van Loon, J.W.A. The application of artificial gravity in medicine and space. Front. Physiol. 2022, 13, 952723.
  36. van Loon, W.A.; Tanck, E.; van Nieuwenhoven, F.; Snoeckx, L.H.E.H.; de Jong, H.A.; Wubbels, R. A brief overview of animal hypergravity studies. J. Gravit. Physiol. 2005, 12, 5–10.
  37. Adamopoulos, K.; Koutsouris, D.; Zaravinos, A.; Lambrou, J.A. Gravitational Influence on Human Living Systems and the Evolution of Species on Earth. Molecules 2021, 26, 2784.
  38. Tominari, T.; Ichimaru, R.; Taniguchi, K.; Yumoto, A.; Shirakawa, M.; Matsumoto, C.; Watanabe, K.; Hirata, M.; Itoh, Y.; Shiba, D.; et al. Hypergravity and microgravity exhibited reversal effects on the bone and muscle mass in mice. Sci. Rep. 2019, 9, 6614.
  39. Yoon, G.; Oh, C.S.; Kim, H.S. Hypergravity upregulates renal inducible nitric oxide synthase expression and nitric oxide productions. Oncotarget 2016, 7, 30147–30154.
  40. Alauzet, C.; Cunat, L.; Wack, M.; Lozniewski, A.; Busby, H.; Agrinier, N.; Cailliez-Grimal, C.; Frippiat, J.-P. Hypergravity disrupts murine intestinal microbiota. Sci. Rep. 2019, 9, 9410.
  41. Lichterfeld, Y.; Kalinski, L.; Schunk, S.; Schmakeit, T.; Feles, S.; Frett, T.; Herrmann, H.; Hemmersbach, R.; Liemersdorf, C. Hypergravity Attenuates Reactivity in Primary Murine Astrocytes. Biomedicines 2022, 10, 1966.
  42. Wade, C.E. Responses across the gravity continuum: Hypergravity to microgravity. Adv. Space Biol. Med. 2005, 10, 225–245.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
This entry is offline, you can click here to edit this entry!
ScholarVision Creations
Feedback