This ground-based program was intended to address the etiology of visual system structural and functional changes observed in astronauts during both inflight and postflight periods. Using the well-documented rat hindlimb suspension (HLS) model, functionally equivalent to human head-down bedrest, we examined the relationship between cephalic fluid shifts resulting from long-duration G-unloading and the regulation of intracranial and intraocular pressures, as well as the effects these same cephalic fluid shifts have on visual system structure and function. Animals were chronically instrumented with biotelemetry to continuously measure intracranial pressure. Additionally, regular intraocular pressure measurements were made by tonometry during long-term exposure to cephalic fluid shifts induced by suspension. MRI images visualizing the visual system morphology were collected from HLS and control animals at regular intervals. Retinal morphology and ultrastructure were examined at specified intervals both during HLS and post-HLS recovery by ophthalmic examinations. This program utilized both male and female subjects in order to examine possible sex differences in these responses. We also examined the possible contributory factors of aging and elevated atmospheric carbon dioxide (hypercapnia) on these responses of the visual system. Further, in addition to mimicking the effects of long duration exposure to microgravity through the use of the HLS model, we examined the responses of our measured outcomes during long-term recovery in the post-HLS period. Collectively, these data will help us to develop a model to both understand and predict the etiology of changes in visual structure and function in astronauts exposed to the microgravity of spaceflight and during postflight recovery. This study investigated the development of a translational mammalian model within the context of hindlimb unloading, sex, and aging by which the data generated using this model can facilitate the development of countermeasures to alleviate any visual system decrements arising from exposure to the microgravity spaceflight environment. This study derives results from Magnetic Resonance Imaging, Optical Coherence Tomography, Tonometry, and A-scan Ultrasonography assays using eye tissues. This study is related to results found in OSD-680 (optic nerve) and OSD-681(subcutaneous tissue and subdural space).