Impact of Spaceflight and Artificial Gravity on the Mouse Retina: Biochemical and Proteomic Analysis

Abstract

Astronauts are reported to have experienced some impairment in visual acuity during their mission on the International Space Station (ISS) and after they returned to Earth. There is emerging evidence that changes in vision may involve alterations in ocular structure and function. To investigate possible mechanisms, changes in protein expression profiles and oxidative stress-associated apoptosis were examined in mouse ocular tissue after spaceflight. Nine-week-old male C57BL/6 mice (n = 12) were launched from the Kennedy Space Center on a SpaceX rocket to the ISS for a 35-day mission. The animals were housed in the mouse Habitat Cage Unit (HCU) in the Japan Aerospace Exploration Agency (JAXA) “Kibo” facility on the ISS. The flight mice lived either under an ambient microgravity condition (µg) or in a centrifugal habitat unit that produced 1 g artificial gravity (µg + 1 g). Habitat control (HC) and vivarium control mice lived on Earth in HCUs or normal vivarium cages, respectively. Quantitative assessment of ocular tissue demonstrated that the µg group induced significant apoptosis in the retina vascular endothelial cells compared to all other groups (p < 0.05) that was 64% greater than that in the HC group. Proteomic analysis showed that many key pathways responsible for cell death, cell repair, inflammation, and metabolic stress were significantly altered in µg mice compared to HC animals. Additionally, there were more significant changes in regulated protein expression in the µg group relative to that in the µg + 1 g group. These data provide evidence that spaceflight induces retinal apoptosis of vascular endothelial cells and changes in retinal protein expression related to cellular structure, immune response and metabolic function, and that artificial gravity (AG) provides some protection against these changes. These retinal cellular responses may affect blood–retinal barrier (BRB) integrity, visual acuity, and impact the potential risk of developing late retinal degeneration.

Spaceflight associated neuro-ocular syndrome (SANS) and the neuro-ophthalmologic effects of microgravity: a review and an update

“…60,78 CONCLUSION In summary, novel and unique neuro-ophthalmic findings have been documented in astronauts during and after LDSF and have been termed SANS. Although a single unifying and overreaching mechanism has yet to be proven, 1,2,[4][5][6][7][8][9]19,40,41,44,[55][56][57] and a multifactorial pathogenesis may be involved, it is likely that SANS may be the end result of cephalad fluid shifts to the brain and orbit brought about by extended MG exposure. Mao et al reviewed the impact of spaceflight and artificial gravity in a mouse retinal model using biochemical and proteomic analysis.…”

“…The interested reader is directed to both our own prior review articles but also the animal and human work performed by the many intramural and extramural NASA related partners working on SANS. [6][7][8][9] Despite the recognition and research related to SANS for many years, several unanswered questions remain: (1) What, if any, is the significance of potential preferential laterality (i.e., right-sided bias) seen in the anatomical changes of SANS? (unpublished data, personal communication WT); (2) Are there changes in the eye's anterior segment (in addition to the posterior segment findings) associated with SANS?…”

“…In the terrestrial environment, CSF is largely produced in the choroid plexus and drains into the lower pressure cervical venous vasculature. [1][2][3][4][5][6][7][8][9] Although vascular autoregulation stabilizes the cerebral and ONH arterial diameter, 10,11 jugular venous distention has been well documented during both head down and microgravity (MG) studies 12 suggesting that cerebral and jugular venous congestion may be present in the MG environment. Jugular venous distention alone does not necessarily prove that venous pressure is increased during spaceflight and some studies have suggested that the venous pressure may in fact be decreased.…”

Validation of a New Rodent Experimental System to Investigate Consequences of Long Duration Space Habitation

“…Recently, the Japanese Space Agency performed important experiments with a newly developed flight hardware system supporting singly-housed mice, which can be centrifuged at 1 g to replace Earth's gravity level while on the ISS 12 . Findings from their experiments reveal that 1 g artificial gravity mitigates the expected bone loss and muscle atrophy 12 as well as retinal changes 13 that occur after long duration microgravity. Each of the various flight hardware systems developed for long duration spaceflight has unique features, which have the potential to influence results obtained ( Table 1).…”

Hypergravity Activates a Pro-Angiogenic Homeostatic Response by Human Capillary Endothelial Cells

“…Based on the literature [59][60][61][62], we expected gene expression changes associated with apoptosis. Indeed, although the experimental treatment was brief, CFLAR, a factor that protects against apoptosis [63], was found up-regulated in HMEC-1 cells upon hypergravity, our result being coherent with data from other cell types [27,64,65].…”