A link between ischemia and mechanical failure in the optic nerve head
Description
Primary open angle glaucoma is a group of diseases responsible for a progressive optic neuropathy that is characterized by cupping of the optic nerve head, thinning of the neuroretinal rim, atrophy of the optic nerve fibers, and visual field loss. It may afflict as many as 67 million people worldwide. It is often, but not always, associated with an increase in intraocular pressure (IOP). There is still no clear etiological understanding of why extensive remodeling of the lamina cribrosa occurs. It is likely that it is multi-factorial and interdependent on several events. The work contained herein investigated the possibility that ischemia in the optic nerve head may trigger the release of biochemical factors from support cells that weaken the lamina cribrosa and lead to neural compression and death through mechanical means Long term studies on low oxygen and nutrient studies revealed that rabbit scleral fibroblasts had higher levels of active MMP-2 in 5% O2 than in 21% O2, and in groups without a medium change than in groups with a regular medium change. Short term studies on other ocular cell types found no difference in total MMP-2. Both studies provided a basis for developing better in vitro models of ischemia Cellular solid models provided a means to relate laminar microstructure to continuum-level properties. Macro-scale stress was amplified above normal levels of IOP in the lamina cribrosa but the stress levels were less than in the peripapillary sclera and in the sclera far from the scleral canal. The most important parameter in determining the IOP-induced stress and strain in the lamina cribrosa was the stiffness of the laminar microstructure relative to the sclera. Predicted strains in a normal lamina, for an increase in IOP of 15 mm Hg to 50 mm Hg, ranged from approximately 0.5 to 5% based on different model parameters. Data obtained from nanoindentation tests suggested that the lamina cribrosa stiffness does little to resist the opening of the scleral canal. Additional work should target the peripapillary sclera and scleral canal to determine if changes in their microstructure could be an important part of glaucomatous damage