Protective Effects of Minocycline and Acetazolamide on Visual Function in Simulated Microgravity Rats

Abstract This study established a tail-suspension rat model to investigate the effects of simulated microgravity on intraocular biomechanical homeostasis and visual function, while evaluating the protective roles of acetazolamide (AZE) and minocycline (MINO). Forty-eight rats were divided into ground control (CTRL, n=12) and simulated microgravity groups (n=36), with the latter further categorized by treatment (PBS, AZE, or MINO) and exposure duration (2 or 4 weeks; n=6/group). Assessments included intraocular pressure (IOP), intracranial pressure (ICP), translaminar cribrosa pressure difference (TLCPD), electroretinography (ERG), optomotor response (OMR), and optical coherence tomography (OCT), supplemented by immunofluorescence staining and Sholl analysis. Simulated microgravity significantly elevated IOP and ICP, altered TLCPD, and induced neuroimmune activation, leading to ERG and OMR impairments. AZE effectively reduced IOP and ICP, mitigating mechanical stress, whereas MINO suppressed microglial and astrocytic activation, attenuating retinal neurodegeneration. ERG and OMR demonstrated that MINO restored photopic negative response (PhNR) amplitudes near control levels by 4 weeks. OCT revealed that both AZE and MINO inhibited retinal thinning, particularly in the outer nuclear layer (ONL). Immunofluorescence confirmed MINO’s suppression of microglial activation and morphological changes. These findings suggest that AZE preserves visual function by modulating intraocular pressure dynamics, while MINO exerts neuroprotection by mitigating neuroinflammation, offering potential dual therapeutic strategies for spaceflight-associated visual impairment.