'Chemical ischemia' in cultured retina cells: the role of excitatory amino acid receptors and of energy levels on cell death.

Abstract

In this study, we determined whether the retina cell death observed in response to an ischemic-like insult is related to an overactivation of the ionotropic glutamate receptors and/or to a collapse of the energy levels. Cultured chick retina cells were submitted to 'chemical ischemia' by metabolic inhibition with sodium cyanide and iodoacetic acid, which block oxidative phosphorylation and glycolysis, respectively. The assessment of neuronal injury was made spectrophotometrically by quantification of cellularly reduced MTT, which gives information about mitochondrial function, or by staining with fluorescein diacetate (FDA), which correlates with changes in the plasma membrane permeability. 'Chemical ischemia' induced both an acute and a delayed time-dependent degeneration of chick retina cells. We observed that 2 min after the ischemic insult, the levels of ATP were reduced to a minimum. On the other hand, the metabolic inhibition induced the release of aspartate, glutamate and gamma-aminobutyric acid, and the activation of AMPA/kainate receptors during the period of metabolic arrest was partially responsible for the loss of mitochondrial function. However, the NMDA and non-NMDA receptor antagonists (MK-801 and CNQX) did not prevent the plasma membrane damage caused by sodium cyanide and iodoacetic acid. The results show that the collapse of the energy levels, rather than the increase in excitatory amino acids, appears to underlie the observed cell injury, suggesting an important relationship between ischemia-induced depletion of high-energy metabolites and retina cell degeneration.

• Authors: I L Ferreira, C B Duarte, A P Carvalho
• Journal: Brain research (Brain Res) Vol. 768 Issue 1-2 Pg. 157-66 (Sep 12 1997) ISSN: 0006-8993 [Print] Netherlands
• PMID: 9369312 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adenine Nucleotides
• Amino Acids
• Excitatory Amino Acid Antagonists
• Potassium Channels
• Receptors, Glutamate
• gamma-Aminobutyric Acid

Topics

• Adenine Nucleotides (metabolism)
• Amino Acids (metabolism)
• Animals
• Cell Death (drug effects)
• Cells, Cultured
• Chick Embryo
• Energy Metabolism (drug effects)
• Excitatory Amino Acid Antagonists (pharmacology)
• Ischemia (chemically induced)
• Membrane Potentials (drug effects)
• Potassium Channels (drug effects)
• Receptors, Glutamate (physiology)
• Retinal Vessels (drug effects, metabolism)
• gamma-Aminobutyric Acid (metabolism)