(P17-003-24) A Mouse Model of Spaceflight Associated Neuro-ocular Syndrome Using One-Carbon Genetics

Objectives: Spaceflight Associated Neuro-ocular Syndrome (SANS) includes an array of ophthalmic and neurologic signs and symptoms observed in a subset of astronauts after prolonged spaceflight. The etiology of these changes remains unknown. Data from spaceflight and bed rest studies provide evidence that the one-carbon (1C) metabolic pathway is involved in the risk of developing SANS. Specifically, it has been demonstrated that genetic variants of methionine synthase reductase (MTRR) A66G and serine hydroxymethyltransferase-1 (SHMT1) C1420T are associated with ophthalmic changes. Moreover, the magnitude of change in total retinal thickness (ΔTRT) in astronauts is greater for those with these genetic variants when combined with lower B-vitamin status (e.g., folate, vitamins B6 and B12, and riboflavin). Rodent research utilizing real and simulated spaceflight conditions has yet to provide a rodent model of SANS.

Methods: In this study, mice with a genetic knock-out (KO) for SHMT1 are compared to age-matched WT mice fed either a folate-deficient (FD) or folate-sufficient (FS) diet. Optical coherence tomography (OCT) is performed to determine TRT. Blood is collected following OCT to assess B-vitamin status. Following the study, the mice will be euthanized, and ocular pathologies will be assessed via histological staining.

Results: Preliminary analyses have indicated an effect of the diet on TRT (FS TRT = 202 μm vs. FD TRT = 243 μm). Additionally, TRT trended high in the SHMT KO fed the FD diet (TRT = 246 μm) as compared to WT on the same diet (TRT = 239 μm). Further OCT analyses are necessary before any conclusions can be drawn regarding observations as a result of diet, genetics, or a combination thereof.

Conclusions: This study will evaluate the relationship between biochemical markers of disrupted one-carbon metabolism and total retinal thickness. Creating rodent models of SANS will allow us to systematically evaluate individual contributing factors of the spaceflight environment (radiation, microgravity, CO₂, etc) that increase one’s risk of developing SANS and allow for the testing and/or evaluation of countermeasures.

Funding Sources: This work is funded by Texas A&M Institute for Advancing Health through Agriculture.