Low dose space radiation-induced effects on the mouse retina and blood-retinal barrier integrity

Abstract

The health risk of flight condition-triggered ocular injury and neurodegeneration has long been a concern. Spaceflight missions will likely expose the astronauts and experiment payloads to greater radiation levels compared to those encountered on the Earth. Knowledge about the susceptibility to adverse effects from low doses of radiation during space missions is very limited. Our present study aims to investigate and compare the effects of whole-body simulated galactic cosmic rays (GCR) on blood-retinal barrier (BRB) integrity, oxidative stress, and apoptosis in the retina of male and female mouse models. Six-month-old male and female CD1 mice were either sham irradiated or received whole-body 5-ion simulated GCR exposure at a dose of 0.5 Gy. At four months following irradiation, mice were euthanized and ocular tissues were collected for histochemical analysis. BRB integrity was evaluated with biomarkers aquaporin-4 (AQP-4), a water channel protein, tight junction (TJ) Zonula occludens-1 (ZO-1), and adhesive molecule, platelet endothelial cell adhesion molecule-1 (PECAM-1). A significantly increased expression of AQP-4 was observed in the retina following GCR exposure compared to controls (p < 0.05) with more pronounced changes observed in the female mice over males. There was also a significant increase in the expression of PECAM-1 and a decrease in the expression of ZO-1 in the retina of irradiated groups compared to controls. Immunochemical analysis revealed enhanced immunoreactivity for oxidative biomarker, 4-hydroxynonenal (4-HNE) in the retina following radiation exposure. Significant increases in the numbers of apoptotic cells were also documented in the retina of irradiated male and female mice compared to controls (p < 0.05). Our study revealed that exposure to low-dose ionizing radiation induced cellular oxidative damage that may alter retina structure and BRB integrity. The results also demonstrate some sex-related differences in the radiation response. Further studies are needed to investigate the factors that contribute to gender- or genetic related variabilities in ocular changes to radiation exposure for a better understanding of the mechanisms of spaceflight-induced ocular findings.