In search of a mouse model of Spaceflight Associated Neuro-ocular Syndrome using one-carbon genetics

Spaceflight Associated Neuro-ocular Syndrome (SANS) represents a group of ocular signs and symptoms affecting some astronauts, with genetic and metabolic factors associated with its development. This study investigated whether genetic disruption of one-carbon metabolism in a murine model, specifically via Shmt1 knockout (KO) and folate restriction (FR), could induce retinal changes mimicking SANS. Wild-type (WT) and Shmt1 KO mice were maintained on either a folate-sufficient (FS) or FR diet, and retinal thickness was assessed via optical coherence tomography at multiple time points. Red blood cell folate concentrations were significantly lower in FR mice but were not further affected by Shmt1 KO. Retinal thickness declined with age in FS WT mice, while FR WT mice exhibited early reductions in retinal thickness, suggesting a congenital effect. Shmt1 KO mice on FR diets showed delayed retinal thinning, potentially due to compensatory metabolic mechanisms. No overt retinal pathology was observed, as expected, without other environmental stressors. These findings suggest that folate availability influences retinal structure and may contribute to SANS susceptibility. Additional research is required to examine the combined impact of diminished folate availability alongside a spaceflight stressor, such as radiation, CO2, or microgravity, on retinal thickness. Such work could potentially lead to a murine model of SANS.