Chronic low-dose glutamate is toxic to retinal ganglion cells. Toxicity blocked by memantine.
Invest Ophthalmol Vis Sci
; 37(8): 1618-24, 1996 Jul.
Article
em En
| MEDLINE
| ID: mdl-8675405
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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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Ganglionares da Retina
/
Memantina
/
Ácido Glutâmico
/
Antagonistas de Aminoácidos Excitatórios
Limite:
Animals
Idioma:
En
Revista:
Invest Ophthalmol Vis Sci
Ano de publicação:
1996
Tipo de documento:
Article
País de afiliação:
Estados Unidos