Understanding mechanisms of pressure-induced optic nerve damage

Patients with glaucoma can suffer progressive vision loss, even in the face of what appears to be excellent intraocular pressure (IOP) control. Some of this may be secondary to non-pressure-related (pressure-independent) factors. However. it is likely, that chronically elevated IOP produces progressive changes in the optic nerve head. the retina. or both that alter susceptibility of remaining optic nerve fibers to IOP. In order to understand the nature of these progressive changes. relevant. cost-effective animal models are necessary. Several rat models are now used to produce chronic, elevated IOP, and methods exist for measuring the resulting IOP and determining the extent of the damage this causes to the retina and optic nerve. A comparison of damage, pressure and duration shows that these models are not necessarily equivalent. These tools are beginning to uncover clear evidence that elevated IOP produces progressive changes in the optic nerve head and retina. In the optic nerve head, these include axonal and non-axonal effects, the latter pointing to involvement of extracellular matrix and astrocyte responses. In the retina, retinal ganglion cells appear to undergo changes in neurotrophin response as well as morphologic changes prior to actual cell death. These. and other, as yet uncovered, abnormalities in the optic nerve head and retina may influence relative susceptibility to IOP and explain progressive optic nerve damage and visual field loss. in spite of apparent. clinically adequate IOP control. Ultimately, this knowledge may lead to the development of new treatments designed to preserve vision in these difficult patients. (C) 2004 Elsevier Ltd. All rights reserved.