Toxins (Mar 2016)

PhTx3-4, a Spider Toxin Calcium Channel Blocker, Reduces NMDA-Induced Injury of the Retina

  • Nancy Scardua Binda,
  • Charles Porto Petruceli Carayon,
  • Rafael Mourão Agostini,
  • Ana Cristina do Nascimento Pinheiro,
  • Marta Nascimento Cordeiro,
  • Marco Aurélio Romano Silva,
  • Juliana Figueira Silva,
  • Elizete Maria Rita Pereira,
  • Claudio Antonio da Silva Junior,
  • Célio José de Castro Junior,
  • Andre Luiz Sena Guimarães,
  • Marcus Vinicius Gomez

DOI
https://doi.org/10.3390/toxins8030070
Journal volume & issue
Vol. 8, no. 3
p. 70

Abstract

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The in vivo neuroprotective effect of PhTx3-4, a spider toxin N-P/Q calcium channel blocker, was studied in a rat model of NMDA-induced injury of the retina. NMDA (N-Methyl-d-Aspartate)-induced retinal injury in rats reduced the b-wave amplitude by 62% ± 3.6%, indicating the severity of the insult. PhTx3-4 treatment increased the amplitude of the b-wave, which was almost equivalent to the control retinas that were not submitted to injury. The PhTx3-4 functional protection of the retinas recorded on the ERG also was observed in the neuroprotection of retinal cells. NMDA-induced injury reduced live cells in the retina layers and the highest reduction, 84%, was in the ganglion cell layer. Notably, PhTx3-4 treatment caused a remarkable reduction of dead cells in the retina layers, and the highest neuroprotective effect was in the ganglion cells layer. NMDA-induced cytotoxicity of the retina increased the release of glutamate, reactive oxygen species (ROS) production and oxidative stress. PhTx3-4 treatment reduced glutamate release, ROS production and oxidative stress measured by malondialdehyde. Thus, we presented for the first time evidence of in vivo neuroprotection from NMDA-induced retinal injury by PhTx3-4 (-ctenitoxin-Pn3a), a spider toxin that blocks N-P/Q calcium channels.

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