An experimental basis for implicating excitotoxicity in glaucomatous optic neuropathy.
Most therapy for glaucoma is directed at the management of the intraocular pressure (IOP). Conventional wisdom holds that excessive pressure within the eye leads to the ganglion cell loss/optic nerve damage seen in this disease. Both glutamate and elevated IOP can selectively damage the retinal ganglion cells in the mammalian eye. We have identified an elevated level of glutamate in the vitreous humor of glaucoma patients (27 microM as compared to 11 microM in the control population). This concentration of glutamate suffices--on its own--to kill retinal ganglion cells. It is plausible that the IOP may represent an initial insult that precipitates the production of excessive glutamate. Therefore, even if glutamate elevation is an epiphenomenon associated with the course of the disease, it may contribute to ganglion cell loss in humans. Lowering the IOP may slow down glutamate production, but if nothing is done to block the toxic effects of glutamate as well, visual loss may result despite excellent IOP control. If interventions can be found to retard the production or toxic effects of glutamate, it may be possible to slow glaucomatous visual loss.
Scheie Eye Institute and Philadelphia Veterans Administration, Department of Ophthalmology, University of Pennsylvania, 19104, USA.
C K
CK
Vorwerk
M S
MS
Gorla
E B
EB
Dreyer
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005901:Glaucoma / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D007429:Intraocular Pressure; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009901:Optic Nerve Diseases / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000473:pathology; D014822:Vitreous Body / Q000378:metabolism
D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D018698:Glutamic Acid; D016202:N-Methylaspartate; D019001:Nitric Oxide Synthase