Lomerizine, a Ca2+ channel blocker, reduces glutamate-induced neurotoxicity and ischemia/reperfusion damage in rat retina

We examined the effects of a new Ca2+ channel blocker, lomerizine, on the i ntraocular hypertension-induced ischemia/reperfusion injury in rat retina a nd on the glutamate-induced neurotoxicity in rat cultured retinal neurons, and compared its effects with those of a Ca2+ channel blocker (flunarizine) and an N-methyl-D-aspartate receptor antagonist (MK-801). Morphometric eva luation at 7 days after ischemia/reperfusion showed that treatment with lom erizine (0.1 and 1 mg kg(-1), i.v.) prior to ischemia and again immediately after reperfusion dose-dependently reduced the retinal damage. Treatment w ith MK-801 (1 mg kg(-1), i.v.) before ischemia significantly reduced the re sulting retinal damage, Flunarizine (0.1 and 1 mg kg(-1), i.v.) tended to r educe the retinal damage, but its effect did not reach statistical signific ance. In an in vitro study, pretreatment with lomerizine (0.1 1 and 1 mu M) or flunarizine (1 mu M) significantly reduced glutamate-induced neurotoxic ity, the effects being concentration dependent. Lomerizine (1 mu M) also ex hibited protective effects against both the N-methyl-D-aspartate and kainat e induced types of neurotoxicity. However, lomerizine (1 mu M) had little e ffect on the neurotoxicity induced by ionomycin (1 mu M) application. Gluta mate-induced neurotoxicity was abolished by removing Ca2+ from the medium. These results indicate that lomerizine protects neuronal cells against reti nal neurotoxicity both in vivo and in vitro, and that this Ca2+ channel blo cker may be useful as a therapeutic drug against retinal diseases that caus e neuronal injury, such as normal tension glaucoma (NTG). (C) 2000 Academic Press.