The mechanisms by which stress and strain affect cellular functions, leading to changes in astrocyte phenotype and glaucomatous optic neuropathy, are not well understood. The disruption of axonal transport observed in glaucoma could be a consequence of cytoskeletal alterations and microtubule loss that result from transient stretch injury,
51 but other cellular functions have also been shown to be affected by stress and strain, including cell adhesion, transmembrane transport, and RNA processing.
52 53 To elucidate the possible relevance of a given level of stress or strain requires the determination of normal physiologic levels. Downs et al.
28 considered a physiologic level of strain in the sclera to be between 0% and 1% and suggested that levels above 3.5% could be pathophysiologic, because they result in detectable changes in scleral material properties (stiffening). Slightly higher strain levels (5%–6%) were sufficient to induce a wide range of biological effects in neuronal cells in in vitro models.
6 54 The same threshold for axonal injury was observed by Margulies and Thibault.
55 Using adult guinea pig optic nerves Bain and Meaney
56 estimated a Lagrangian strain threshold of 21% for morphologic axonal injury and 18% for deterioration of nerve function. These values are lower than the 27.1% measured in infant guinea pigs.
57 Using a mixture of experiments and computational models of a guinea pig brain Anderson
58 developed a probabilistic model of injury based on the peak von Mises stress in a region. Stresses of 27 to 43 kPa (202–322 mm Hg) resulted in 50% chance of injury in up to 20% of the affected region. Variable shear stress, such as may occur in tissue during diurnal variations in IOP, leads to injury in three times more cells than does steady shear stress.
59
The peak levels of strain and stress predicted by our models exceed most of the thresholds just quoted. Some of the extreme strains and stresses predicted by the models are due to nonphysiologic geometric details (e.g., nonrounded “corners”); however, strain levels in the LC in particular are nontrivial, consistent with the hypothesis that mechanical effects can contribute to damage to nerve fibers and loss of visual function observed in glaucoma.