 |
 Previous Article | Next Article 
Journal of Neuroscience, Vol 11, 966-971, Copyright © 1991 by Society for Neuroscience
N-methyl-D-aspartate antagonists prevent kainate neurotoxicity in rat retinal ganglion cells in vitro
NJ Sucher, E Aizenman and SA Lipton
Department of Neurology, Children's Hospital, Boston, Massachusetts 02115.
Under defined culture conditions, exogenous glutamate (Glu), NMDA, or an
endogenous Glu-related toxin is lethal to rat retinal ganglion cells; these
detrimental effects are NMDA receptor mediated because specific NMDA
antagonists can prevent cellular injury. In the presence of an endogenous
Glu-like toxin, 125 microM kainate (KA) increases the proportion of retinal
ganglion cells that die, but the toxicity (due to both KA and the
endogenous toxin) is totally prevented by 2-amino-5- phosphonovalerate
(APV), a specific NMDA receptor antagonist. These findings indicate that
the KA-induced portion of retinal ganglion cell death also appears to be
mediated via NMDA receptors. There are at least 2 possible mechanisms for
this lethal effect. In addition to KA receptors, KA could directly
stimulate NMDA receptors. Alternatively, KA might activate its own specific
receptor, which in turn leads to a net increase in the release of an
endogenous Glu-related toxin; this endogenous substance would then activate
NMDA receptors. Patch-clamp electrophysiology experiments have helped to
distinguish between these possibilities. Concentrations of APV that
completely block the current elicited by maximal nondesensitizing doses of
NMDA exert no detectable inhibition of KA-evoked currents. Hence, at the
concentrations used, it appears unlikely that KA directly activates NMDA
receptors in this preparation. Furthermore, the fraction of toxicity
attributed to the addition of KA can be blocked by the relatively specific
non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). This
finding is consistent with the hypothesis that KA adds an increment of
toxicity in this system by directly interacting with KA receptors.(ABSTRACT
TRUNCATED AT 250 WORDS)
This article has been cited by other articles:
|
|
|
|
 
A. T. E. Hartwick, C. M. Hamilton, and W. H. Baldridge
Glutamatergic calcium dynamics and deregulation of rat retinal ganglion cells
J. Physiol.,
July 15, 2008;
586(14):
3425 - 3446.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Fan, X. Li, and N. G. F. Cooper
CaMKII{alpha}B Mediates a Survival Response in Retinal Ganglion Cells Subjected to a Glutamate Stimulus
Invest. Ophthalmol. Vis. Sci.,
August 1, 2007;
48(8):
3854 - 3863.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Wamsley, B. T. Gabelt, D. B. Dahl, G. L. Case, R. W. Sherwood, C. A. May, M. R. Hernandez, and P. L. Kaufman
Vitreous Glutamate Concentration and Axon Loss in Monkeys With Experimental Glaucoma
Arch Ophthalmol,
January 1, 2005;
123(1):
64 - 70.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. A. Hare, E. WoldeMussie, R. K. Lai, H. Ton, G. Ruiz, T. Chun, and L. Wheeler
Efficacy and Safety of Memantine Treatment for Reduction of Changes Associated with Experimental Glaucoma in Monkey, I: Functional Measures
Invest. Ophthalmol. Vis. Sci.,
August 1, 2004;
45(8):
2625 - 2639.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. J. Sucher, K. Kohler, L. Tenneti, H.-k. Wong, T. Grunder, S. Fauser, T. Wheeler-Schilling, N. Nakanishi, S. A. Lipton, and E. Guenther
N-Methyl-D-Aspartate Receptor Subunit NR3A in the Retina: Developmental Expression, Cellular Localization, and Functional Aspects
Invest. Ophthalmol. Vis. Sci.,
October 1, 2003;
44(10):
4451 - 4456.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Honkanen, S. Baruah, M. B. Zimmerman, C. L. Khanna, Y. K. Weaver, J. Narkiewicz, R. Waziri, K. M. Gehrs, T. A. Weingeist, H. C. Boldt, et al.
Vitreous Amino Acid Concentrations in Patients With Glaucoma Undergoing Vitrectomy
Arch Ophthalmol,
February 1, 2003;
121(2):
183 - 188.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Kawasaki, M.-H. Han, J.-Y. Wei, K. Hirata, Y. Otori, and C. J. Barnstable
Protective Effect of Arachidonic Acid on Glutamate Neurotoxicity in Rat Retinal Ganglion Cells
Invest. Ophthalmol. Vis. Sci.,
June 1, 2002;
43(6):
1835 - 1842.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. N. Osborne, J. P. M. Wood, A. Cupido, J. Melena, and G. Chidlow
Topical Flunarizine Reduces IOP and Protects the Retina against Ischemia-Excitotoxicity
Invest. Ophthalmol. Vis. Sci.,
May 1, 2002;
43(5):
1456 - 1464.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Mizuno, T. Koide, M. Yoshimura, and M. Araie
Neuroprotective Effect and Intraocular Penetration of Nipradilol, a {beta}-Blocker with Nitric Oxide Donative Action
Invest. Ophthalmol. Vis. Sci.,
March 1, 2001;
42(3):
688 - 694.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
T. W. Kim, K. B. Kang, H.-K. Choung, K. H. Park, and D. M. Kim
Elevated Glutamate Levels in the Vitreous Body of an In Vivo Model of Optic Nerve Ischemia
Arch Ophthalmol,
April 1, 2000;
118(4):
533 - 536.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
