Glaucoma is a disease of the visual system that, in many cases, is characterized by an elevation of intraocular pressure (IOP), progressive changes in the appearance of the optic disc and retinal nerve fiber layer, and visual field defects. The disease process is thought to originate with the optic nerve as it exits the eye, where it undergoes mechanical, vascular, and/or biochemical injury due to the increased pressure. The result is not just damage to the optic nerve, but also retrograde degeneration of the parent retinal ganglion cells within the retina itself, as well as their target neurons in the visual thalamus.
Previously, we combined intracellular recording and staining techniques with confocal microscopy to examine the structure-function relations that characterize ganglion cell degeneration in glaucoma. Currently, we are using a cat optic nerve crush model to examine the effects that brain-derived neurotrophic factor (BDNF), a potent neuroprotectant, has on the structural and functional integrity of ganglion cells in the vertebrate retina, and the extent to which normal structure and function might be preserved using different neuroprotection-based treatment strategies. These studies combine standard histological techniques, intracellular methods, non-invasive visual testing, and molecular analyses of the injured and treated neurons.The long-range goal is the development of a treatment strategy that mitigates any degenerative changes and preserves a greater level of visual function than is now possible.
Our recent studies have shown that BDNF not only prevents ganglion cell death following optic nerve injury, but that it also preserves the structural and functional integrity of these neurons. In addition, these studies also indicate that providing BDNF to both the eye and brain provides a significantly greater level of neuroprotection compared with the traditional approach of treating the eye alone, thus indicating a need to ‘think beyond the eye’ in the development of long-term neuroprotection strategies for treating glaucoma and other optic neuropathies.
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