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

• Published in: Toxins 2016-03, Vol.8 (3), p.70
• Main Authors: Binda, Nancy Scardua, Carayon, Charles Porto Petruceli, Agostini, Rafael Mourão, Pinheiro, Ana Cristina do Nascimento, Cordeiro, Marta Nascimento, Silva, Marco Aurélio Romano, Silva, Juliana Figueira, Pereira, Elizete Maria Rita, da Silva Junior, Claudio Antonio, de Castro Junior, Célio José, Guimarães, Andre Luiz Sena, Gomez, Marcus Vinicius
• Format: Article
• Language: English
• Subjects: Animals; Calcium Channel Blockers - pharmacology; Calcium Channel Blockers - therapeutic use; Electroretinography; Glutamic Acid - metabolism; Lipid Peroxidation - drug effects; Male; N-Methylaspartate; Neuropeptides - pharmacology; Neuropeptides - therapeutic use; Neuroprotection; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; phoneutria nigriventer; PhTx3-4; Rats, Wistar; Reactive Oxygen Species - metabolism; retina; Retinal Diseases - chemically induced; Retinal Diseases - drug therapy; Retinal Diseases - metabolism; Retinal Diseases - physiopathology; spider toxins; Spider Venoms - pharmacology; Spider Venoms - therapeutic use; Vitreous Body - metabolism
• ISSN: 2072-6651; 2072-6651
• DOI: 10.3390/toxins8030070

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.