Abstract
The health risks associated with spaceflight-induced ocular structural and functional damage has become a recent concern for NASA. The goal of the present study was to characterize the effects of spaceflight and reentry to 1 g on the structure and integrity of the retina and blood-retinal barrier (BRB) in the eye. To investigate possible mechanisms, changes in protein expression profiles were examined in mouse ocular tissue after spaceflight. Ten week old male C57BL/6 mice were launched to the International Space Station (ISS) on Space-X 12 at the Kennedy Space Center (KSC) on August, 2017. After a 35-day mission, mice were returned to Earth alive. Within 38 +/− 4 hours of splashdown, mice were euthanized and ocular tissues were collected for analysis. Ground control (GC) and vivarium control mice were maintained on Earth in flight hardware or normal vivarium cages respectively. Repeated intraocular pressure (IOP) measurements were performed before the flight launch and re-measured before the mice were euthanized after splashdown. IOP was significantly lower in post-flight measurements compared to that of pre-flight (14.4–19.3 mmHg vs 16.3–20.3 mmHg) (p < 0.05) for the left eye. Flight group had significant apoptosis in the retina and retinal vascular endothelial cells compared to control groups (p < 0.05). Immunohistochemical analysis of the retina revealed that an increased expression of aquaporin-4 (AQP-4) in the flight mice compared to controls gave strong indication of disturbance of BRB integrity. There were also a significant increase in the expression of platelet endothelial cell adhesion molecule-1 (PECAM-1) and a decrease in the expression of the BRB-related tight junction protein, Zonula occludens-1 (ZO-1). Proteomic analysis showed that many key proteins and pathways responsible for cell death, cell cycle, immune response, mitochondrial function and metabolic stress were significantly altered in the flight mice compared to ground control animals. These data indicate a complex cellular response that may alter retina structure and BRB integrity following long-term spaceflight.
Highlights
Astronaut health and safety are of key importance to the success of long-term missions in space
The purpose of this study was to characterize the effects of spaceflight on the retinal vasculature and possible alterations in blood-retinal barrier (BRB) integrity, and to identify spaceflight-induced proteomic significance and biomarkers in mouse ocular tissue
The data demonstrate that spaceflight induces apoptosis in the retinal vascular endothelial cells and photoreceptors (Fig. 2), as well as evokes alterations in vascular levels of AQP-4 (Fig. 3), platelet endothelial cell adhesion molecule-1 (PECAM-1) (Fig. 4) and Zonula occludens-1 (ZO-1) (Fig. 5), proteins related to BRB integrity
Summary
Astronaut health and safety are of key importance to the success of long-term missions in space. Little work has been done to examine retinal structure and BRB integrity/function following prolonged exposure to spaceflight in animal models. Spaceflight has been reported to have numerous negative effects on ocular and structure and function[3]. Numerous differences were noted in the flight mice compared to control animals on ground, an intriguing finding especially relevant to the present study was that spaceflight conditions induced significant changes in protein expression related to endothelial apoptosis, inflammation and metabolic function in the retina. The goal of the present study was to characterize the effects of spaceflight on retinal vascular alterations and BRB integrity, and to identify changes in protein expression profiles in mouse ocular tissue following spaceflight using immunohistochemistry (IHC) and a proteomics approach
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