Simulation of murine retinal hemodynamics in response to tail suspension

Abstract

The etiology of spaceflight-associated neuro-ocular syndrome (SANS) remains unclear. Recent murine studies indicate there may be a link between the space environment and retinal endothelial dysfunction. Post-fixed control (N = 4) and 14-day tail-suspended (TS) (N = 4) mice eye samples were stained and imaged for the vessel plexus and co-located regions of endothelial cell death. A custom workflow combined whole-mounted and tear reconstructed three-dimensional (3D) spherical retinal plexus models with computational fluid dynamics (CFD) simulation that accounted for the Fåhræus-Lindqvist effect and boundary conditions that accommodated TS fluid pressure measurements and deeper capillary layer blood flow distribution. TS samples exhibited reduced surface area (4.6 ± 0.5 mm² vs. 3.5 ± 0.3 mm², P = 0.010) and shorter lengths between branches in small vessels (<10 μm, 69.5 ± 0.6 μm vs. 60.4 ± 1.1 μm, P < 0.001). Wall shear stress (WSS) and pressure were higher in TS mice compared to controls, particularly in smaller vessels (<10 μm, WSS: 6.57 ± 1.08 Pa vs. 4.72 ± 0.67 Pa, P = 0.034, Pressure: 72.04 ± 3.14 mmHg vs. 50.64 ± 6.74 mmHg, P = 0.004). Rates of retinal endothelial cell death were variable in TS mice compared to controls. WSS and pressure were generally higher in cell death regions, both within and between cohorts, but significance was variable and limited to small to medium-sized vessels (<20 μm). These findings suggest a link may exist between emulated microgravity and retinal endothelial dysfunction that may have implications for SANS development. Future work with increased sample sizes of larger species or spaceflight cohorts should be considered.

Keywords: Cell death; Computational fluid dynamics; Mouse; Retina; SANS; Tail suspension.