Vinpocetine regulates cation channel permeability of inner retinal neurons in the ischaemic retina

•Metabolic insult increases cation channel permeability of inner retinal neurons.•Vinpocetine reduces cation channel permeability in some neurons during ischemia.•Vinpocetine prevents loss of Ca2+ binding protein labeling during metabolic insult.•Vinpocetine alters cation channel permeability in NMDA but not kainate activation.•Vinpocetine’s actions may involve NMDA glutamate receptors and intracellular Ca2+.

Vinpocetine is a natural drug which exerts neuroprotective effects in ischaemia of the brain through actions on cation channels, glutamate receptors and other pathways. This study investigated the effect of vinpocetine on cation channel permeability of inner retinal neurons after acute retinal metabolic insult. We focused on amacrine and ganglion cells immunoreactive for calretinin or parvalbumin due to their previously documented susceptibility to ischaemia. Using the probe, 1-amino-4-guanidobutane (AGB), we observed increased cation channel permeability across amacrine and ganglion cells under ischaemia and hypoglycaemia but not anoxia. Calretinin and parvalbumin immunoreactivity was also reduced during ischaemia and hypoglyacemia but not anoxia. Vinpocetine decreased AGB entry into ischaemic and hypoglycaemic ganglion cells indicating that the drug can modulate unregulated cation entry. In addition, vinpocetine prevented the loss of calretinin and parvalbumin immunoreactivity following ischaemia suggesting it may indirectly regulate intracellular calcium. Vinpocetine also reduced AGB permeability in selected amacrine and ganglion cell populations following N-methyl-D-aspartate (NMDA) but not kainate activation suggesting that vinpocetine’s regulation of cation channel permeability may partly involve NMDA sensitive glutamate receptors.

Graphical abstractDamage by retinal ischaemia includes increased cation channel permeability and decreased calretinin (and other calcium binding proteins) immunoreactivity. Treatment with vinpocetine reduces unregulated cation entry and recovers calretinin labelling to near normal levels.Figure optionsDownload full-size imageDownload as PowerPoint slide