Primary open-angle glaucoma (POAG) is characterized by progressive cupping of the optic disc and posterior displacement and compression of the lamina cribrosa (LC), usually associated with elevated intraocular pressure (IOP). Coincidental topographically- related optic nerve axonal loss correlates with retinal ganglion cell apoptosis, retinal nerve fiber bundle thinning and visual field damage. While the clinical features of POAG are well established, the underlying mechanisms by which neuropathy occurs remain elusive, especially the relative importance of mechanical vs. vascular factors-an area we are addressing.
Using a novel non-linear optical approach and short-pulse lasers, we have shown that:
- The adult LC (scleral portion of the optic nerve head) is a three dimensionally complex portion of the lower visual pathway through which bundles of ganglion cell axons transit in route to the brain.
- Elevated intraocular pressure deforms or stretches the ONH tissues, and in particular, the LC. These changes lead to misalignment of pores between the LC beams, causing pinching and distortion of nerve fiber bundles within the LC.
Our NEI sponsored experimental evidence suggests that LC deformation may alter local vascular flow, compromise axonal function, and activate matrix remodeling. We suggest that differences in the mechanical characteristics of the ONH between individuals might account for the remarkable clinical variability in their susceptibility to intraocular pressure-induced damage.
In collaboration with the University of Pittsburgh, our data is being used to modify and refine mechanical models of the ONH. These models are being developed to improve our understanding of how individuals respond to IOP and are helping to develop better methods to predict and individuals? risk for POAG. We hope this will aid clinicians in better predicting susceptibility and allow for earlier intervention to preserve sight.
Posted April 2013