Figure 10.

Postmortem EG versus control eye differences in LMA reflect both passive connective tissue deformation (vertical axis) and active connective tissue synthesis, remodeling, and mechanical failure (horizontal axis). For a given ONH, the magnitude of deformation (increasing up) and the magnitude of connective tissue synthesis and remodeling (increasing to the right) govern the character of detected postmortem EG versus control eye differences in LMA. Animal age (as a surrogate for stiff versus compliant tissues and/or senescent versus robust cells at any age) and the magnitude of IOP insult (both bottom left and upper right) independently influence both the magnitude of deformation and the character of the connective tissue response. In the absence of any active connective tissue response (lower and upper left), LC deformation alone should result in passive thinning of the LC beams and passive expansion of the pores. Once deformed, mechanoreceptors within LC beam fibroblasts and astrocytes should drive connective tissue synthesis and remodeling. From a beam that was acutely thinned due to deformation, if beam synthesis leads to a return to predeformation BD, there will be no detected EG versus control eye BD difference; yet the number of connective tissue voxels will have increased. Beyond synthesis alone, where there is connective tissue remodeling and recruitment (lower and upper, middle), there may be increases or decreases in the number of detected connective tissue voxels. Finally, where connective tissue synthesis and remodeling are not adequate, mechanical failure and connective tissue degradation may ensue (lower and upper, right), leading to a reduction in detected connective tissue voxels. Where beams have disappeared, pore enlargement that is not due to passive pore expansion may be detected. Age may influence both connective tissue material properties (more compliant when young, stiffer when old) and the vigor of the synthesis/remodeling response (more robust in the young, senescent when old). For a given magnitude of postlaser IOP insult, age should both influence the magnitude of deformation and the character of the connective tissue response. The magnitude and independence of these age and IOP effects need to be confirmed in larger longitudinal studies of in vivo LMA and material properties.