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Protective Effect of Retinal Ischemia by Blockers of Voltage-dependent Calcium Channels and Intracellular Calcium Stores

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Abstract

In the present study, the neuroprotective effect of blockers of voltage-dependent calcium channels (VDCC) and intracellular calcium stores on retinal ischemic damage induced by oxygen deprivation-low glucose insult (ODLG) was investigated. Retinal damage induced by ODLG was dependent on the calcium concentration in the perfusion medium. When incubated in medium containing 2.4 mM CaCl2, cell death in ischemic retinal slices treated with blockers of VDCC, ω-conotoxin GVIA (1.0 μM), ω-conotoxin MVIIC (100 nM) and nifedipine (1.0 μM), was reduced to 62 ± 2.3, 46 ± 4.3 and 47 ± 3.9%, respectively. In the presence of blockers of intracellular calcium stores, dantrolene (100 μM) and 2-APB (100 μM), the cell death was reduced to 46 ± 3.2 and 55 ± 2.9%, respectively. Tetrodotoxin (1.0 μM), reducing the extent of the membrane depolarization reduces the magnitude of calcium influx trough VDCC causing a reduction of the cell death to 55 ± 4.3. Lactate dehydrogenase content of untreated ischemic retinal slices was reduced by 37% and treatment of ischemic slices with BAPTA-AM (100 μM) or 2-APB (100 μM) abolished the leakage of LDH. Dantrolene (100 μM) and nifedipine (1.0 μM) partially blocked the induced reduction on the LDH content of retinal ischemic slices. Histological analysis of retinal ischemic slices showed 40% reduction of ganglion cells that was prevented by BAPTA-AM or dantrolene. 2-APB partially blocked this reduction whilst nifedipine had no effect, p > 0.95. Conclusion Blockers of VDCC and intracellular calcium-sensitive receptors exert neuroprotective effect on retinal ischemia.

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Acknowledgement

Supported by Instituto do Milenio, CNPq, Capes, Pronex and Fapemig.

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Authors and Affiliations

  1. Nucleo Pós Graduação Santa Casa, Belo Horizonte, MG, Brazil

    Pindaro Dias Massote & Marcus Vinicius Gomez

  2. Departamento de Farmacologia, ICB, UFMG, Belo Horizonte, MG, Brazil

    Ana Cristina Nascimento Pinheiro, Marco Antonio Máximo Prado & Marcus Vinicius Gomez

  3. Departamento de Morfologia, ICB, UFMG, Belo Horizonte, MG, Brazil

    Cristina Guatimosim Fonseca

  4. Departamento de Dentistica, Universidade Estadual Montes Claros, Montes Claros, MG, Brazil

    André L. S. Guimarães

  5. Departamento de Fisiologia e Biofísica, ICB, UFMG, Belo Horizonte, MG, Brazil

    André R. Massensini

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  1. Pindaro Dias Massote
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  2. Ana Cristina Nascimento Pinheiro
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  3. Cristina Guatimosim Fonseca
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  4. Marco Antonio Máximo Prado
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  5. André L. S. Guimarães
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  6. André R. Massensini
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  7. Marcus Vinicius Gomez
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Correspondence to Marcus Vinicius Gomez.

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Massote, P.D., Pinheiro, A.C.N., Fonseca, C.G. et al. Protective Effect of Retinal Ischemia by Blockers of Voltage-dependent Calcium Channels and Intracellular Calcium Stores. Cell Mol Neurobiol 28, 847–856 (2008). https://doi.org/10.1007/s10571-007-9243-0

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  • DOI: https://doi.org/10.1007/s10571-007-9243-0

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