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
Affiliations
Nancy Scardua Binda
Institute of Education and Research Santa Casa Belo Horizonte-Laboratory of Toxins, Rua Domingos Vieira 590, Belo Horizonte, Minas Gerais 30150-240, Brazil
Charles Porto Petruceli Carayon
Institute of Education and Research Santa Casa Belo Horizonte-Laboratory of Toxins, Rua Domingos Vieira 590, Belo Horizonte, Minas Gerais 30150-240, Brazil
Rafael Mourão Agostini
Institute of Education and Research Santa Casa Belo Horizonte-Laboratory of Toxins, Rua Domingos Vieira 590, Belo Horizonte, Minas Gerais 30150-240, Brazil
Ana Cristina do Nascimento Pinheiro
Institute of Education and Research Santa Casa Belo Horizonte-Laboratory of Toxins, Rua Domingos Vieira 590, Belo Horizonte, Minas Gerais 30150-240, Brazil
Marta Nascimento Cordeiro
Ezequiel Dias Foundation (FUNED), Laboratory of Biochemistry, Rua Conde Pereira Carneiro 80, Belo Horizonte, Minas Gerais 30510-010, Brazil
Marco Aurélio Romano Silva
Faculty of Medicine, Minas Gerais Federal University, Neuroscience Laboratory, Av. Alfredo Balena 190, Belo Horizonte, Minas Gerais 30130-100, Brazil
Juliana Figueira Silva
Institute of Education and Research Santa Casa Belo Horizonte-Laboratory of Toxins, Rua Domingos Vieira 590, Belo Horizonte, Minas Gerais 30150-240, Brazil
Elizete Maria Rita Pereira
Institute of Education and Research Santa Casa Belo Horizonte-Laboratory of Toxins, Rua Domingos Vieira 590, Belo Horizonte, Minas Gerais 30150-240, Brazil
Claudio Antonio da Silva Junior
Institute of Education and Research Santa Casa Belo Horizonte-Laboratory of Toxins, Rua Domingos Vieira 590, Belo Horizonte, Minas Gerais 30150-240, Brazil
Célio José de Castro Junior
Institute of Education and Research Santa Casa Belo Horizonte-Laboratory of Toxins, Rua Domingos Vieira 590, Belo Horizonte, Minas Gerais 30150-240, Brazil
Andre Luiz Sena Guimarães
Department of Dentistry, Montes Claros State University, University Hospital, Health Laboratory Research, Montes Claros, Montes Claros, Minas Gerais 39401-001, Brazil
Marcus Vinicius Gomez
Institute of Education and Research Santa Casa Belo Horizonte-Laboratory of Toxins, Rua Domingos Vieira 590, Belo Horizonte, Minas Gerais 30150-240, Brazil
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.
