Protective effect of donepezil on retinal ganglion cells in vitro and in vivo.
The neuroprotective effect of donepezil, an acetylcholinesterase inhibitor on retinal ganglion cells (RGCs), was examined. The survival of purified RGCs after exposure to glutamate with or without donepezil (10(- 7) M to 10(- 5) M) was measured after 3 days in culture. In vivo, the neuroprotective effect of donepezil was examined by quantifying the number of viable RGCs 7 days after axotomy in adult rats. In vitro, donepezil dose-dependently reduced RGC death caused by glutamate toxicity. Oral administration of donepezil (10 mg kg(-1) day(-1)) significantly reduced RGC death after axotomy. In conclusion, donepezil exerts a protective effect on RGCs both in vitro and in vivo.
Miki
Atsuya
A
Department of Ophthalmology and Visual Science, Osaka University Medical School, Suita, Osaka, Japan.
Otori
Yasumasa
Y
Morimoto
Takeshi
T
Okada
Masaki
M
Tano
Yasuo
Y
D000284:Administration, Oral; D000818:Animals; D019771:Axotomy; D001578:Benzopyrans / Q000494:pharmacology; D002470:Cell Survival; D002478:Cells, Cultured; D018680:Cholinergic Antagonists / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D019610:Cytoprotection; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D018698:Glutamic Acid / Q000633:toxicity; D007189:Indans / Q000494:pharmacology*; D008464:Mecamylamine / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009570:Nitriles / Q000494:pharmacology; D020221:Optic Nerve Injuries / Q000473:pathology; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000473:pathology; D012601:Scopolamine / Q000494:pharmacology
D001578:Benzopyrans; D018680:Cholinergic Antagonists; D002800:Cholinesterase Inhibitors; D004791:Enzyme Inhibitors; D007189:Indans; D018696:Neuroprotective Agents; D009570:Nitriles; D010880:Piperidines; C456800:ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate; D018698:Glutamic Acid; D008464:Mecamylamine; D000077265:Donepezil; D012601:Scopolamine