July 1996
Volume 37, Issue 8
Free
Articles  |   July 1996
Chronic low-dose glutamate is toxic to retinal ganglion cells. Toxicity blocked by memantine.
Author Affiliations
  • C K Vorwerk
    Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA.
  • S A Lipton
    Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA.
  • D Zurakowski
    Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA.
  • B T Hyman
    Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA.
  • B A Sabel
    Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA.
  • E B Dreyer
    Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA.
Investigative Ophthalmology & Visual Science July 1996, Vol.37, 1618-1624. doi:
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    • Get Citation

      C K Vorwerk, S A Lipton, D Zurakowski, B T Hyman, B A Sabel, E B Dreyer; Chronic low-dose glutamate is toxic to retinal ganglion cells. Toxicity blocked by memantine.. Invest. Ophthalmol. Vis. Sci. 1996;37(8):1618-1624.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

PURPOSE: It is well known that acute exposure to high concentrations of glutamate is toxic to central mammalian neurons. However, the effect of a chronic, minor elevation over endogenous glutamate levels has not been explored. The authors have suggested that such chronic exposure may play a role in glaucomatous neuronal loss. In the current study, they sought to explore whether a chronic, low-dose elevation in vitreal glutamate was toxic to retinal ganglion cells and whether this toxicity could be prevented with memantine, a glutamate antagonist. METHODS: Rats were injected serially and intravitreally with glutamate to induce chronic elevations in glutamate concentration. A second group of rats was treated with intraperitoneal memantine and glutamate. Control groups received vehicle injection with or without concurrent memantine therapy. After 3 months, the animals were killed, and ganglion cell survival was evaluated. RESULTS: Intravitreal injections raised the intravitreal glutamate levels from an endogenous range of 5 to 12 microM glutamate to 26 to 34 microM. This chronic glutamate elevation killed 42% of the retinal ganglion cells after 3 months. Memantine treatment alone had no effect on ganglion cell survival. However, when memantine was given concurrently with low-dose glutamate, memantine was partially protective against glutamate toxicity. CONCLUSIONS: These data suggest that minor elevations in glutamate concentration can be toxic to ganglion cells if this elevation is maintained for 3 months. Furthermore, memantine is efficacious at protecting ganglion cells from chronic low-dose glutamate toxicity.

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