title: NMDA receptor subunits have different roles in NMDA-induced neurotoxicity in the retina.
abstract: BACKGROUND
  Loss of retinal ganglion cells (RGCs) is a hallmark of various retinal diseases including glaucoma, retinal ischemia, and diabetic retinopathy. N-methyl-D-aspartate (NMDA)-type glutamate receptor (NMDAR)-mediated excitotoxicity is thought to be an important contributor to RGC death in these diseases. Native NMDARs are heterotetramers that consist of GluN1 and GluN2 subunits, and GluN2 subunits (GluN2A-D) are major determinants of the pharmacological and biophysical properties of NMDARs. All NMDAR subunits are expressed in RGCs in the retina. However, the relative contribution of the different GluN2 subunits to RGC death by excitotoxicity remains unclear.
  
  
  RESULTS
  GluN2B- and GluN2D-deficiency protected RGCs from NMDA-induced excitotoxic retinal cell death. Pharmacological inhibition of the GluN2B subunit attenuated RGC loss in glutamate aspartate transporter deficient mice.
  
  
  CONCLUSIONS
  Our data suggest that GluN2B- and GluN2D-containing NMDARs play a critical role in NMDA-induced excitotoxic retinal cell death and RGC degeneration in glutamate aspartate transporter deficient mice. Inhibition of GluN2B and GluN2D activity is a potential therapeutic strategy for the treatment of several retinal diseases.
authors.affiliation: Laboratory of Molecular Neuroscience, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan. bai.ning.aud@mri.tmd.ac.jp
authors.forename: Ning
authors.initials: N
authors.lastname: Bai
authors.forename: Tomomi
authors.initials: T
authors.lastname: Aida
authors.forename: Michiko
authors.initials: M
authors.lastname: Yanagisawa
authors.forename: Sayaka
authors.initials: S
authors.lastname: Katou
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakimura
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Mishina
authors.forename: Kohichi
authors.initials: K
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D027341:Excitatory Amino Acid Transporter 1 / Q000172:deficiency / Q000378:metabolism; D017353:Gene Deletion; D020287:In Situ Nick-End Labeling; D007546:Isoquinolines / Q000494:pharmacology; D051379:Mice; D016202:N-Methylaspartate / Q000633:toxicity*; D009498:Neurotoxins / Q000633:toxicity*; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012160:Retina / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*
chemical_list: C513822:7-hydroxy-6-methoxy-2-methyl-1-(2-(4-(trifluoromethyl)phenyl)ethyl)-1,2,3,4-tetrahydroisoquinoline hydrochloride; D027341:Excitatory Amino Acid Transporter 1; D007546:Isoquinolines; D009498:Neurotoxins; D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate; C493393:Slc1a3 protein, mouse; D016202:N-Methylaspartate
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