[The effect of gabapentin and gabapentin-lactam on retinal ganglion cell survival. Situation after acute retinal ischemia in animal models].

BACKGROUND

Reduction in the excitatory and potentially toxic neurotransmitter glutamate can protect retinal ganglion cells. What are the effects of the antiepileptic drug gabapentin, for which antiglutamatergic effects have been described, and the new substance gabapentin-lactam (GBP-L) on retinal ganglion cell survival after retinal ischemia?

METHODS

In 3 groups of 10 rats each, ischemia was induced by elevating the intraocular pressure of the left eye to 120 mmHg for 1 h. Saline, gabapentin (2 x 50 mg/kg intraperitoneally) and GBP-L (2 x 50 mg/kg intraperitoneally) were injected before and 5 h after ischemia. Two weeks later ischemic damage was quantified histologically by counting the number of neurons in the ganglion cell layer. In vitro transmitter release experiments were performed to obtain information on the effect of gabapentin and GBP-L on ischemia-induced glutamate release and the mechanism of action of GBP-L.

RESULTS

In the control group 17% of the retinal ganglion cells survived ischemia. GBP-L doubled the number of the surviving cells while gabapentin was not effective in these experiments. In vitro gabapentin and GBP-L reduced ischemia-induced glutamate release by 35.7% and 42.5%, respectively. The blockade of ATP-sensitive potassium channels antagonized the effect of GBP-L completely.

CONCLUSION

GBP-L is neuroprotective in retinal ischemia and diminishes the release of the excitatory neurotoxic amino acid glutamate. The effect of GBP-L might be mediated by ATP-sensitive potassium channels. Also gabapentin reduced glutamate release but was not neuroprotective in vivo.