Diltiazem-induced Neuroprotection in Glutamate Excitotoxicity and Ischemic Insult of Retinal Neurons

Abstract

These results are consistent with previous studies suggesting that Ca(2+) channel activation contributes to retinal cell death following either glutamate excitotoxicity or retinal ischemia. Under both conditions, the L-type Ca(2+) channel blocker, diltiazem, can limit cell death. These results extend the potential application of diltiazem in retinal neuroprotection to retinal pathologies involving glutamate excitotoxicity and ischemia.

Progesterone inhibition of neuronal calcium signaling underlies aspects of progesterone-mediated neuroprotection

“…Calcium imaging and electrophysiological approaches revealed that this progesterone-mediated neuroprotection occurs via direct inhibition of voltage-gated calcium channel function. These data are consistent with studies that have implicated calcium channels in glutamate-induced cell death [74; 75; 76]. Since the concentrations of progesterone needed to achieve inhibition of L-type channels (IC 50 = 27 μM) are far in excess of those needed to activate the progestin receptor [77], expression of the receptor is likely not necessary for these observed effects of progesterone.…”

Effect of Flunarizine, a Calcium Channel Blocker, on Intraocular Pressure and Aqueous Humor Dynamics in Monkeys

“…22 This potential neuroprotective effect of flunarizine has been studied in a variety of experimental models, including ischemia-reperfusion models in rabbits, 3 rats, 33 sheep, 17 and gerbils 21 ; in sciatic 20 and optic 19 nerve axotomy in rats; and in a model of light-mediated injury to the rat retina. 18 Calcium antagonists have also been reported to be neuroprotective in ischemia-reperfusion models in vivo 34,35 and in excitotoxicity models in which retinal ganglion cells and cortical neurons in cell culture were exposed to N-methyl-D-aspartate and glutamate 3,35 or in which nerve growth factor was withdrawn. 20 In addition, the effect of this class of agents on vascular smooth muscle could contribute to the improvement in optic nerve head or retinal blood flow measured in normal subjects and in patients with glaucoma after treatment with calcium channel blockers, 9,15,16,28 and to the improvement in visual field parameters observed in patients with normal tension glaucoma.…”

Progesterone inhibition of voltage-gated calcium channels is a potential neuroprotective mechanism against excitotoxicity

“…These secondary sources of calcium strongly contribute to calcium overload, and thus also have an essential role in excitotoxicity. One calcium channel subtype in particular, the L-type calcium channel, appears to play an essential role in glutamate-induced cell death, as inhibition of this channel following the induction of excitotoxicity is highly neuroprotective [15–17]. …”