Intraocular Pressure and Retinal Nerve Fiber Layer Changes in a Microgravity Mouse Model and Relevance to Spaceflight-Associated Neuro-Ocular Syndrome

Purpose: Microgravity-induced headward fluid shifts are one of the mechanisms implicated in spaceflight-associated eye conditions, including intraocular pressure (IOP) and retinal nerve fiber layer (RNFL) thickness changes. In this longitudinal study, we investigated IOP and RNFL thickness changes over time in a mouse model of microgravity-induced headward fluid shifts. Methods: /J mice, randomly assigned to two groups: the hindlimb unloading (HU) mice, unloaded for 21 days followed by 14 days of release, and control mice kept under the same conditions except HU for 35 days. IOP and RNFL thickness in peripapillary and peripheral rings of right and left eyes were measured before and once a week after HU. Our analysis utilized mixed linear models to compare the estimated marginal means of IOP and RNFL thickness on each day with baseline values for each eye. Post hoc splined mixed linear models with a knot at day 14 were employed to assess the rate of IOP change in each segment. Results: IOP was significantly elevated in both eyes of the HU mice on day 14 compared to baseline. The splined analysis revealed a bilateral positive rate of IOP change up to day 14, followed by a negative rate of change thereafter. In contrast, control mice displayed no significant differences in IOP at any timepoint. RNFL thicknesses of right eye peripapillary and peripheral rings were reduced after 1 week and 2 weeks, respectively. In contrast, left eye RNFL thickness measurements did not show any significant change compared to baseline. Conclusion: The HU mouse model displays a distinct ocular phenotype that may be useful for understanding IOP and RNFL changes in microgravity and their relevance to Spaceflight-Associated Neuro-ocular Syndrome.