Journal Article

NMDA receptor subunits have different roles in NMDA-induced neurotoxicity in the retina

Bai, Ning, Mishina, Masayoshi, Tanaka, Kohichi, Aida, Tomomi, Katou, Sayaka, Sakimura, Kenji, Yanagisawa, Michiko

2013

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V
• Subject: Animals / Apoptosis / Biomedical and Life Sciences / Biomedicine / Brain research / Cell Death - drug effects / Diabetic retinopathy / Excitatory Amino Acid Transporter 1 - deficiency / Excitatory Amino Acid Transporter 1 - metabolism / Experiments / Gene Deletion / In Situ Nick-End Labeling / Ischemia / Isoquinolines - pharmacology / Methyl aspartate / Mice / N-Methylaspartate - toxicity / Neural receptors / Neurology / Neurosciences / Neurotoxicity syndromes / Neurotoxins - toxicity / Permeability / Physiological aspects / Polymerase chain reaction / Protein Subunits - antagonists & inhibitors / Protein Subunits - metabolism / Proteins / Psychopharmacology / Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors / Receptors, N-Methyl-D-Aspartate - metabolism / Retina / Retina - drug effects / Retina - metabolism / Retina - pathology / Retinal diseases / Rodents / Science