TY - JOUR
T1 - Characterization of mouse ocular response to a 35-day spaceflight mission
T2 - Evidence of blood-retinal barrier disruption and ocular adaptations
AU - Mao, Xiao W.
AU - Nishiyama, Nina C.
AU - Byrum, Stephanie D.
AU - Stanbouly, Seta
AU - Jones, Tamako
AU - Drew, Alyson
AU - Sridharan, Vijayalakshmi
AU - Boerma, Marjan
AU - Tackett, Alan J.
AU - Zawieja, David
AU - Willey, Jeffrey S.
AU - Delp, Michael
AU - Pecaut, Michael J.
N1 - Publisher Copyright:
© 2019, The Author(s).
PY - 2019/6/3
Y1 - 2019/6/3
N2 - 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.
AB - 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.
KW - Intraocular Pressure
KW - Mice, Inbred C57BL
KW - Blood-Retinal Barrier/physiology
KW - Male
KW - Space Flight
KW - Adaptation, Ocular
KW - Glial Fibrillary Acidic Protein/metabolism
KW - Animals
KW - Endothelial Cells/metabolism
KW - Zonula Occludens-1 Protein/metabolism
KW - Eye Proteins/metabolism
KW - Platelet Endothelial Cell Adhesion Molecule-1/metabolism
KW - Aquaporin 4/metabolism
KW - Proteomics
KW - Crystallins/metabolism
KW - Mice
KW - Apoptosis
KW - Cluster Analysis
UR - https://www.scopus.com/pages/publications/85066624631
UR - https://www.scopus.com/pages/publications/85066624631#tab=citedBy
UR - https://www.mendeley.com/catalogue/7954c5ad-73c5-3639-889d-ae1b5fc4ad36/
U2 - 10.1038/s41598-019-44696-0
DO - 10.1038/s41598-019-44696-0
M3 - Article
C2 - 31160660
SN - 2045-2322
VL - 9
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 8215
ER -