Memantine is neuroprotective in a rat model of pressure-induced retinal ischemia.
OBJECTIVE
To quantify vitreous amino acid concentrations in pressure-induced retinal ischemia and to evaluate the neuroprotective effect of memantine, a N-methyl-D-aspartate (NMDA) antagonist, administered before and at two time intervals after ischemia.


METHODS
Retinal ischemia was induced in 10 rats by elevating the intraocular pressure to 120 mm Hg. The concentrations of the amino acids of vitreous samples were measured by high-pressure liquid chromatography. In another series of 56 rats, ischemia was induced in a similar fashion. Fifteen rats received 20 mg/kg x day memantine by a subcutaneous osmotic pump starting 2 days before ischemia, 13 rats received 10 mg/kg memantine intraperitoneally (ip) 0.5 and 4.5 hours after reperfusion, 13 rats received 10 mg/kg memantine ip 3.5 and 7.5 hours after reperfusion, and 15 rats received the vehicle alone. Ischemic damage was histologically quantified 14 days after ischemia.


RESULTS
Compared with the nonischemic fellow eyes, there was an elevation (P < 0.05) in the mean vitreous concentration of glutamate (223%+/-41%) and glycine (428%+/-92%). The percentage of surviving neurons in the ganglion cell layer was 33%+/-3% in the controls, 61%+/-5% (P < 0.001) when memantine was infused subcutaneously before ischemia, 52%+/-5% (P < 0.05) when memantine was injected ip 0.5 and 4.5 hours after ischemia, and 48%+/-5% (P > 0.05) when injected ip 3.5 and 7.5 hours after ischemia.


CONCLUSIONS
Retinal ischemia increased vitreous concentrations of glutamate and glycine. Both amino acids were agonists at the NMDA receptor. The NMDA receptor antagonist memantine reduced ganglion cell loss when given systemically before or within 30 minutes of retinal ischemia.
Lagrèze
W A
WA
Department of Ophthalmology, Albert-Ludwigs Universität, Freiburg, Germany.
Knörle
R
R
Bach
M
M
Feuerstein
T J
TJ
D000818:Animals; D002452:Cell Count; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D007429:Intraocular Pressure; D007511:Ischemia / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008559:Memantine / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D009798:Ocular Hypertension / Q000150:complications; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012171:Retinal Vessels; D014822:Vitreous Body / Q000378:metabolism
D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D016202:N-Methylaspartate; D005998:Glycine; D008559:Memantine