Phoneutria spider toxins block ischemia-induced glutamate release and neuronal death of cell layers of the retina

Retina. 2011 Jul-Aug;31(7):1392-9. doi: 10.1097/IAE.0b013e318205b249.

Abstract

Purpose: To investigate the effect of calcium channel blockers, spider toxins, on cell viability and the glutamate content of ischemic retinal slices.

Methods: Rat retinal slices were subjected to ischemia via exposure to oxygen-deprived low-glucose medium for 45 minutes. Slices were either treated or not treated with the toxins PhTx3, Tx3-3, and Tx3-4. After oxygen-deprived low-glucose insult, glutamate content and cell viability were assessed in the slices by confocal and optical microscopy.

Results: In the retinal ischemic slices that were treated with PhTx3, Tx3-3, and Tx3-4, confocal imaging showed a decrease in cell death of 79.5 ± 3.1%, 75.5 ± 5.8%, and 61 ± 3.8%, respectively. Neuroprotective effects were also observed 15, 30, 60, and 90 minutes after the onset of the retinal ischemic injury. As a result of the ischemia, glutamate increased from 6.2 ± 1.0 nMol/mg protein to 13.2 ± 1.0 nMol/mg protein and was inhibited by PhTx3, Tx3-3, and Tx3-4 to 8.6 ± 0.7, 8.8 ± 0.9, and 7.4 ± 0.8 nMol/mg protein, respectively. Histologic analysis of the live cells in the outer, inner, and ganglion cell layers of the ischemic slices showed a considerable reduction in cell death by the toxin treatment.

Conclusion: Spider toxins reduced glutamate content and cell death of retinal ischemic slices.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Channel Blockers / pharmacology
  • Cell Death / drug effects
  • Cell Survival / drug effects
  • Glutamic Acid / metabolism*
  • Microscopy, Confocal
  • Neuropeptides / pharmacology*
  • Neuroprotective Agents / pharmacology
  • Neurotoxins / pharmacology*
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / prevention & control*
  • Retinal Diseases / metabolism
  • Retinal Diseases / prevention & control*
  • Retinal Neurons / drug effects*
  • Spider Venoms / pharmacology*

Substances

  • Calcium Channel Blockers
  • Neuropeptides
  • Neuroprotective Agents
  • Neurotoxins
  • Spider Venoms
  • Tx3 neurotoxin
  • Glutamic Acid