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We developed a physiologically detailed lumped\u2010parameter model coupling a five\u2010compartment retinal vascular network with a dynamic intraocular pressure module responsive to hydrostatic shifts. Head\u2010down tilt experiments were reproduced to emulate cephalad fluid shifts in microgravity. Model outputs are closely aligned with experimental benchmarks. Intraocular pressure increased from 16.3\u00a0mmHg (upright) to 29.5\u00a0mmHg at \u221230\u00b0 (81% increase), while ocular perfusion pressure remained within 2\u00a0mmHg, reflecting haemodynamic responses. Retinal blood\u2010flow predictions fell within the interquartile range of\n                      <jats:italic>in vivo<\/jats:italic>\n                      Doppler measurements, and peak systolic velocity trends in the central retinal artery agreed within 1% of ultrasound data after incorporating a microgravity\u2010induced 4% central retinal artery constriction. These findings validate the model's ability to capture the coupled influence of systemic arterial pressure, venous drainage and intraocular pressure on retinal perfusion across gravitational states. Simulations revealed that posture\u2010induced elevations in arterial pressure and intraocular pressure propagate non\u2010linearly through the retinal tree, imposing the greatest mechanical stress on the central retinal artery and arteriolar segments, critical sites for flow dysregulation and potential optic nerve damage. By integrating retinal and ocular biomechanics, the model developed in this work offers mechanistic insight into the pathogenesis of neuro\u2010ocular syndrome, establishes quantitative thresholds to inform countermeasure development, and provides a transferable tool for terrestrial disorders involving intraocular pressure and vascular dysregulation, such as glaucoma and hypertensive retinopathy.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp70402-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Microgravity and postural changes alter ocular circulation, contributing to spaceflight\u2010associated neuro\u2010ocular syndrome (SANS), yet their impact on retinal haemodynamicsremains poorly characterized.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We present a lumped\u2010parameter model that dynamically couples intraocular pressure (IOP) with retinal blood flow through a five\u2010compartment vascular network.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The model simulates posture\u2010induced hydrostatic changes and accurately reproduces trends in IOP, ocular perfusion pressure and retinal flow observed in head\u2010down tilt experiments.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Simulations reveal that arterial compartments (especially the central retinal artery) are the most sensitive to gravitational stress and vascular constriction, identifying key sites of haemodynamic vulnerability.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>This framework provides novel mechanistic insights into the retinal contributions to SANS and offers a validated platform for evaluating countermeasures and studying ocular pathologies.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  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