Overview of the experimental procedure used in this study. (A) an example of the harvested eye [OD] and surrounding tissue with labeling for anatomical orientation [I=inferior, N=nasal, S=superior, T=temporal]. (B) Posterior segment of an eyeball [OS] showing the four anatomical quadrants. (C) An eye with the optic nerve transected flush with the posterior scleral surface. (D) A tangential slice of an ONH (scale bar = 1 mm), from which four samples (E; scale bar = 0.1 mm) are harvested (one from each quadrant). (F) Each sample was tested using a micromechanical compression testing system, and the height [h] and width [a] of the sample were measured throughout the test (scale bar = 0.1 mm). From these measurements, the axial and lateral strains (engineering strains) were calculated as ϵaxial =h/h0 −1 and ϵlateral =a/a0 −1, respectively, and the apparent Poisson’s ration was computed as νapp = −ϵlateral/ϵaxial; note that the axial direction is approximately normal to the optic disk (G) An axisymmetric finite element model was used to model the mechanical response of the ONH, where a rigid plate compresses the ONH sample in the axial (axis-3) direction. Rolling boundary conditions were utilized at the bottom and center-line to enforce model symmetry. The lateral face of the sample was prescribed to have zero pressure, which allowed outflow of fluid during compression.