Expression of N-methyl-d-aspartate receptor 1 in rats with chronic ocular hypertension.
High levels of glutamate can be toxic to retinal ganglion cells (RGCs). This study investigated the relationship between the N-methyl-d-aspartate receptor 1 (NR) and RGC death in a rat model of chronic ocular hypertension (COHT). COHT was induced in one eye of each rat by episcleral vein cauterization. Retinal protein expression was evaluated at 1, 3, 5 and 9 weeks after cauterization. Quantitative real-time polymerase chain reaction and Western blot analysis showed that NR1 expression was significantly increased in cauterized retinae. NR1 immunoreactivity was observed in the inner nuclear layer (INL) and ganglion cell layer (GCL) in the retina of rats with COHT. RGC density was evaluated after retrograde labeling with fluoro-gold (FG) and 4-di-10-ASP (DiA). A significant decrease in RGC density was observed in ocular hypertensive eyes, and NR1 expression in the GCL suggested an important role of NR1 in the death of RGCs. Memantine (10 mg/kg), an N-methyl-d-aspartate receptor antagonist, was administered orally once daily for up to 5 weeks, while rats in the control group received vehicle phosphate-buffered saline only. Treatment with memantine resulted in a significant reduction in RGC loss and NR1 expression in the eyes of rats COHT. These findings suggest that excessive expression of NR1 is involved in RGC death in glaucoma.
Kim
J H
JH
Department of Ophthalmology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Socho-ku, Seoul 137-701, Korea.
Lee
N Y
NY
Jung
S W
SW
Park
C K
CK
D000704:Analysis of Variance; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D007429:Intraocular Pressure / Q000187:drug effects / Q000502:physiology; D008297:Male; D008559:Memantine / Q000627:therapeutic use; D009798:Ocular Hypertension / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000473:pathology; D013266:Stilbamidines; D013997:Time Factors
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D018691:Excitatory Amino Acid Antagonists; C409466:NR1 NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D013266:Stilbamidines; D008559:Memantine