The excitotoxicity theory of glaucoma

Abstract

Glaucoma can be defined as a disease in which one of the pathophysiological consequences of raised intra-ocular pressure is damage of the optic nerve, and subsequently the loss of retinal ganglion cells (RGCs). One of the main aims of modern glaucoma therapy is to alter the intraocular pressure, either surgically or pharmacologically. Recently it was shown that the vitreous of glaucoma patients contains increased levels of glutamate (27 microM as compared to 11 microM in controls). This concentration of glutamate is sufficient to induce retinal ganglion cell death. The rise in intraocular pressure is probably the initial insult, which enhances the increase or release of glutamate. Although the increase in intravitreal glutamate levels is an accompanying feature of glaucoma, it could contribute to the loss of retinal ganglion cells in humans itself. Therefore, despite efficient control of intra-ocular pressure, RGC's loss will continue resulting in further visual impairment, if the toxic effect of glutamate is not blocked. If it would be possible to understand the mechanism leading to excessive vitreous levels of glutamate in glaucoma or to block its toxic effects, then the resulting visual loss could be retarded. This review discusses various proposed mechanisms leading to intraocular glutamate toxicity and the role of neuroprotection in this disease. (Literature search by Medline).