The Impact of Hindlimb Suspension on the Rat Eye: A Molecular and Histological Analysis of the Retina

Abstract The Spaceflight Associated Neuro-ocular Syndrome (SANS) is hypothesized to be associated with microgravity-induced fluid shifts. There is a need for an animal model of SANS to investigate its pathophysiology. We used the rat hindlimb suspension (HS) model to examine the relationship between the assumed cephalad fluid shifts, intraocular (IOP) pressure and the molecular responses in the retina to the prolonged change in body posture. Long evans rats were subjected to HS up to 90 days. Animals completing 90-day suspension were further studied for recovery periods up to 90 additional days in normal posture. With respect to baseline, the average IOP increase in HS animals and the rate of change varied by cohort. Transcriptomics evidence supported a response to HS in the rat retina that was affected by age and sex. Several molecular networks suggested stress imposed by HS affected the retinal vasculature, oxidative and inflammation status, pigmented epithelium and glia. The CSNK1A1-TP53 pathway was implicated in the response in all cohorts. Sex-specific genes were involved in cytoprotection and may explain sex-dependent vulnerabilities to certain eye diseases. These results support the hypothesis that changes in the biology of the retina subjected to simulated microgravity involve both the neural and vascular retina.