Protective effect of arachidonic acid on glutamate neurotoxicity in rat retinal ganglion cells

Atsushi Kawasaki, Ming Hu Han, Ji Ye Wei, Keiji Hirata, Yasumasa Otori, Colin Barnstable

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

PURPOSE. LOW concentrations of excitotoxic agents such as glutamate decrease survival of retinal ganglion cells (RGCs) and may be an important cause of RGC death in a variety of retinal diseases. Arachidonic acid (AA), an intercellular messenger in the central nervous system, has been reported to have multiple effects on glutamate receptors, including an inhibitory effect on non-N-methyl-D-aspartate (NMDA) receptors. The purpose of this study was to test the hypothesis that AA could protect RGCs from glutamate neurotoxicity. METHODS. RGCs were purified from the rat retina on postnatal days 7 and 8 by a modified two-step panning method. Survival of RGCs after exposure to glutamate, with or without AA treatment, was measured after 3 days in culture. To visualize calcium signals, RGCs were loaded with a calcium indicator dye, fluo-3 acetoxymethyl ester, and the fluorescence was measured by laser scanning confocal microscopy. Electrophysiological effects of AA on non-NMDA ionotropic receptors were examined by using whole-cell patch clamp configurations. RESULTS. Incubation of RGCs with 25 μM glutamate caused 60% loss of RGCs. This glutamate neurotoxicity was significantly ameliorated by low concentrations of AA. Concentrations of AA above 10 μM were toxic to RGCs. Calcium imaging showed that glutamate-, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid- (AMPA) and kainate-induced intracellular calcium accumulation in these cells was reduced by AA. Electrophysiological recordings revealed that currents mediated by non NMDA ionotropic receptors were inhibited by AA in a dose dependent manner. CONCLUSIONS. Low concentrations of AA can reduce glutamate neurotoxicity to RGCs by the inhibition of non-NMDA ionotropic receptors. These results suggest that endogenous or exogenous AA may be used to protect RGCs from glutamate neurotoxicity and that AA may be one potential treatment for RGC loss in a variety of eye diseases, including glaucoma.

Original languageEnglish (US)
Pages (from-to)1835-1842
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume43
Issue number6
StatePublished - Jun 13 2002

Fingerprint

Retinal Ganglion Cells
Arachidonic Acid
Glutamic Acid
D-Aspartic Acid
Calcium
Retinal Diseases
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Eye Diseases
Kainic Acid
Poisons
Glutamate Receptors
N-Methyl-D-Aspartate Receptors
Confocal Microscopy
Glaucoma
Retina
Esters
Cell Death
Coloring Agents
Central Nervous System
Fluorescence

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Kawasaki, Atsushi ; Han, Ming Hu ; Wei, Ji Ye ; Hirata, Keiji ; Otori, Yasumasa ; Barnstable, Colin. / Protective effect of arachidonic acid on glutamate neurotoxicity in rat retinal ganglion cells. In: Investigative Ophthalmology and Visual Science. 2002 ; Vol. 43, No. 6. pp. 1835-1842.
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abstract = "PURPOSE. LOW concentrations of excitotoxic agents such as glutamate decrease survival of retinal ganglion cells (RGCs) and may be an important cause of RGC death in a variety of retinal diseases. Arachidonic acid (AA), an intercellular messenger in the central nervous system, has been reported to have multiple effects on glutamate receptors, including an inhibitory effect on non-N-methyl-D-aspartate (NMDA) receptors. The purpose of this study was to test the hypothesis that AA could protect RGCs from glutamate neurotoxicity. METHODS. RGCs were purified from the rat retina on postnatal days 7 and 8 by a modified two-step panning method. Survival of RGCs after exposure to glutamate, with or without AA treatment, was measured after 3 days in culture. To visualize calcium signals, RGCs were loaded with a calcium indicator dye, fluo-3 acetoxymethyl ester, and the fluorescence was measured by laser scanning confocal microscopy. Electrophysiological effects of AA on non-NMDA ionotropic receptors were examined by using whole-cell patch clamp configurations. RESULTS. Incubation of RGCs with 25 μM glutamate caused 60{\%} loss of RGCs. This glutamate neurotoxicity was significantly ameliorated by low concentrations of AA. Concentrations of AA above 10 μM were toxic to RGCs. Calcium imaging showed that glutamate-, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid- (AMPA) and kainate-induced intracellular calcium accumulation in these cells was reduced by AA. Electrophysiological recordings revealed that currents mediated by non NMDA ionotropic receptors were inhibited by AA in a dose dependent manner. CONCLUSIONS. Low concentrations of AA can reduce glutamate neurotoxicity to RGCs by the inhibition of non-NMDA ionotropic receptors. These results suggest that endogenous or exogenous AA may be used to protect RGCs from glutamate neurotoxicity and that AA may be one potential treatment for RGC loss in a variety of eye diseases, including glaucoma.",
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Protective effect of arachidonic acid on glutamate neurotoxicity in rat retinal ganglion cells. / Kawasaki, Atsushi; Han, Ming Hu; Wei, Ji Ye; Hirata, Keiji; Otori, Yasumasa; Barnstable, Colin.

In: Investigative Ophthalmology and Visual Science, Vol. 43, No. 6, 13.06.2002, p. 1835-1842.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Protective effect of arachidonic acid on glutamate neurotoxicity in rat retinal ganglion cells

AU - Kawasaki, Atsushi

AU - Han, Ming Hu

AU - Wei, Ji Ye

AU - Hirata, Keiji

AU - Otori, Yasumasa

AU - Barnstable, Colin

PY - 2002/6/13

Y1 - 2002/6/13

N2 - PURPOSE. LOW concentrations of excitotoxic agents such as glutamate decrease survival of retinal ganglion cells (RGCs) and may be an important cause of RGC death in a variety of retinal diseases. Arachidonic acid (AA), an intercellular messenger in the central nervous system, has been reported to have multiple effects on glutamate receptors, including an inhibitory effect on non-N-methyl-D-aspartate (NMDA) receptors. The purpose of this study was to test the hypothesis that AA could protect RGCs from glutamate neurotoxicity. METHODS. RGCs were purified from the rat retina on postnatal days 7 and 8 by a modified two-step panning method. Survival of RGCs after exposure to glutamate, with or without AA treatment, was measured after 3 days in culture. To visualize calcium signals, RGCs were loaded with a calcium indicator dye, fluo-3 acetoxymethyl ester, and the fluorescence was measured by laser scanning confocal microscopy. Electrophysiological effects of AA on non-NMDA ionotropic receptors were examined by using whole-cell patch clamp configurations. RESULTS. Incubation of RGCs with 25 μM glutamate caused 60% loss of RGCs. This glutamate neurotoxicity was significantly ameliorated by low concentrations of AA. Concentrations of AA above 10 μM were toxic to RGCs. Calcium imaging showed that glutamate-, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid- (AMPA) and kainate-induced intracellular calcium accumulation in these cells was reduced by AA. Electrophysiological recordings revealed that currents mediated by non NMDA ionotropic receptors were inhibited by AA in a dose dependent manner. CONCLUSIONS. Low concentrations of AA can reduce glutamate neurotoxicity to RGCs by the inhibition of non-NMDA ionotropic receptors. These results suggest that endogenous or exogenous AA may be used to protect RGCs from glutamate neurotoxicity and that AA may be one potential treatment for RGC loss in a variety of eye diseases, including glaucoma.

AB - PURPOSE. LOW concentrations of excitotoxic agents such as glutamate decrease survival of retinal ganglion cells (RGCs) and may be an important cause of RGC death in a variety of retinal diseases. Arachidonic acid (AA), an intercellular messenger in the central nervous system, has been reported to have multiple effects on glutamate receptors, including an inhibitory effect on non-N-methyl-D-aspartate (NMDA) receptors. The purpose of this study was to test the hypothesis that AA could protect RGCs from glutamate neurotoxicity. METHODS. RGCs were purified from the rat retina on postnatal days 7 and 8 by a modified two-step panning method. Survival of RGCs after exposure to glutamate, with or without AA treatment, was measured after 3 days in culture. To visualize calcium signals, RGCs were loaded with a calcium indicator dye, fluo-3 acetoxymethyl ester, and the fluorescence was measured by laser scanning confocal microscopy. Electrophysiological effects of AA on non-NMDA ionotropic receptors were examined by using whole-cell patch clamp configurations. RESULTS. Incubation of RGCs with 25 μM glutamate caused 60% loss of RGCs. This glutamate neurotoxicity was significantly ameliorated by low concentrations of AA. Concentrations of AA above 10 μM were toxic to RGCs. Calcium imaging showed that glutamate-, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid- (AMPA) and kainate-induced intracellular calcium accumulation in these cells was reduced by AA. Electrophysiological recordings revealed that currents mediated by non NMDA ionotropic receptors were inhibited by AA in a dose dependent manner. CONCLUSIONS. Low concentrations of AA can reduce glutamate neurotoxicity to RGCs by the inhibition of non-NMDA ionotropic receptors. These results suggest that endogenous or exogenous AA may be used to protect RGCs from glutamate neurotoxicity and that AA may be one potential treatment for RGC loss in a variety of eye diseases, including glaucoma.

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