Neuroprotective effect of calcium channel blocker against retinal ganglion cell damage under hypoxia.
The purpose of this study was to determine whether iganidipine, nimodipine and lomerizine, potentially useful calcium channel blockers for ophthalmic treatment, have direct retinal neuroprotective effects against hypoxic damage in experimental in vitro model. We used purified retinal ganglion cells (RGCs) from newborn rats. RGCs were incubated in controlled-atmosphere incubator in which oxygen levels were reduced to 5% normal partial pressure and cell viability was assessed. We also examined the effect of calcium channel blockers on the calcium ion concentration in RGC under hypoxic stress by calcium imaging. Iganidipine, nimodipine and lomerizine (0.01-1 microM) increased the RGC viability. Increase in intra-RGC calcium ion concentration by hypoxic damage was reduced by these calcium channel blockers. In conclusion, iganidipine, nimodipine and lomerizine were effective against hypoxic RGC damage in vitro. This neuroprotective effect was thought to be mediated by blocking calcium ion influx into RGC. These findings suggest that iganidipine, nimodipine and lomerizine have a direct neuroprotective effect against RGC damage related to hypoxia.
Yamada
Hideyuki
H
Department of Ophthalmology, Tokyo National Hospital Organization, 3-1-1 Takeoka, Kiyose, Tokyo 204-8585, Japan. yamachan-tky@umin.ac.jp
Chen
Yi-Ning
YN
Aihara
Makoto
M
Araie
Makoto
M
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015687:Cell Hypoxia / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D012165:Retinal Ganglion Cells / Q000187:drug effects*
D002121:Calcium Channel Blockers; D007476:Ionophores; D018696:Neuroprotective Agents; D015759:Ionomycin