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March 1996

Elevated Glutamate Levels in the Vitreous Body of Humans and Monkeys With Glaucoma

Author Affiliations

From the Glaucoma Consultation Service, Massachusetts Eye and Ear Infirmary (Dr Dreyer), the Departments of Neurology (Drs Dreyer and Lipton) and Research Computing and Biostatistics (Dr Zurakowski), Children's Hospital, the Departments of Neurology, Beth Israel Hospital (Dr Lipton), Brigham and Women's Hospital (Dr Lipton), and Massachusetts General Hospital (Dr Lipton), the Departments of Ophthalmology (Dr Dreyer) and Neurology (Dr Lipton), Harvard Medical School, Boston, Mass; and the Department of Ophthalmology, Mount Sinai School of Medicine, New York, NY (Drs Schumer and Podos).; Dr Dreyer is a consultant to Glaxo Corp, Research Triangle Park, NC. Dr Podos is a consultant to Allergan Inc, Irvine, Calif, Alcon Laboratories Inc, Fort Worth, Tex, and Pharmos Corp, Alachua, Fla.

Arch Ophthalmol. 1996;114(3):299-305. doi:10.1001/archopht.1996.01100130295012

Objective:  To explore the possibility that the excitatory amino acid glutamate might be associated with the disease process of glaucoma, which is characterized by the death of retinal ganglion cell neurons and subsequent visual dysfunction.

Methods:  Amino acid analyses were performed on vitreous specimens that were obtained from patients who were undergoing cataract extraction. Samples were collected prospectively from those patients who sustained inadvertent rupture of the posterior capsule between 1988 and 1993. An additional set of specimens, obtained from both eyes of monkeys, was analyzed; in these monkeys, glaucoma had been experimentally induced in one eye only.

Results:  A twofold elevation in the level of glutamate was detected in the vitreous body of the group of patients with glaucoma when compared with that in a control population of patients with cataracts only. An even greater elevation of the glutamate level was found in the vitreous body of glaucomatous eyes of monkeys when compared with that in control eyes. No statistical differences were detected among other amino acid levels from the vitreous body of glaucomatous and nonglaucomatous eyes in humans or monkeys.

Conclusions:  The excitatory amino acid glutamate is found in the vitreous body of glaucomatous eyes at concentrations that are potentially toxic to retinal ganglion cells. The increased level of this known neurotoxin is consistent with an "excitotoxic" mechanism for the retinal ganglion cell and optic nerve damage in glaucoma. Therapies to protect neurons against glutamate toxic effects may prove to be useful in the management of this blinding disease.

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