Impact of microgravity on retinal neuroimmune responses and visual dysfunction in rats.

AIM: To analyze visual dysfunction in rats under simulated weightlessness (SW) by examining trans-laminar cribrosa pressure difference (TLCPD) and neuroimmune responses. METHODS: The 72 male Sprague-Dawley rats were randomly assigned into two groups (ground control and hindlimb unloading-simulated microgravity) using stratified randomization, with each group further subdivided into three exposure durations: SW 2-week (SW-2W), 4-week (SW-4W), and 8-week (SW-8W), n=12 per subgroup. At the designated time points for each group, intraocular pressure (IOP) and intracranial pressure (ICP) were measured, and the trans-laminar cribrosa pressure difference (TLCPD) was calculated. Additionally, optomotor response (OMR), electroretinography (ERG), and optical coherence tomography (OCT) were performed. The number of retinal ganglion cells (RGCs) was quantified via immunofluorescence, the activation of astrocytes and microglial cells was determined, and Sholl analysis was conducted to assess the function and morphology of microglial cells. Data were analyzed with SPSS and GraphPad Prism (P<0.05). RESULTS: Under prolonged simulated microgravity, rats exhibited a progressive increase in both IOP and ICP, with the most pronounced rise observed at 8wk. Concurrently, the TLCPD shifted from a negative value in controls to a positive value. These pressure alterations were associated with retinal dysfunction, as evidenced by significant reductions in ERG b-wave and photopic negative response (PhNR) amplitudes. OCT and histological analyses revealed subtle photoreceptor layer damage: while the inner nuclear layer (INL) thickness remained relatively unchanged, the outer nuclear layer (ONL) thinned significantly, and the nerve fiber layer-ganglion cell layer complex thickness (NFL-GCL) complex initially thickened before later thinning. Immunofluorescence further demonstrated marked neuroimmune activation, with astrocytes transitioning from having large cell bodies with small, elongated, sparse processes to a phenotype characterized by compact, enlarged nuclei and aggregated processes, alongside notable RGC loss. CONCLUSION: Based on the results from the simulated microgravity rat model, microgravity-induced changes in dual-chamber pressure, and neuroimmune responses in the retina may play a key role in visual dysfunction. Specifically, the activation of retinal neuroimmune cells (astrocytes and microglial cells) induced by mechanical stress appears to be central to retinal and optic nerve damage.