The effect of gabapentin and gabapentin-lactam on retinal ganglion cell survival in an animal model of in acute retina ischemia

Background. Reduction in the excitatory and potentially toxic neurotransmit ter glutamate can protect retinal ganglion cells. What are the effects of t he 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, gabapenti n (2x50 mg/kg intraperitoneally) and GBP-L (2x50 mg/kg intraperitoneally) w ere injected before and 5 h after ischemia. Two weeks later ischemic damage was quantified histologically by counting the number of neurons in the gan glion cell layer. In vitro transmitter release experiments were performed t o obtain information on the effect of gabapentin and GBP-L on ischemia-indu ced glutamate release and the mechanism of action of GBP-L. Results. In the control group 17% of the retinal ganglion cells survived is chemia. GBP-L doubled the number of the surviving cells while gabapentin wa s not effective in these experiments. In vitro gabapentin and GBP-L reduced ischemia-induced glutamate release by 35.7% and 42.5%, respectively. The b lockade 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 G BP-L might be mediated by ATP-sensitive potassium channels. Also gabapentin reduced glutamate release but was not neuroprotective in vivo.