NMDA‐induced retinal injury is mediated by an endoplasmic reticulum stress‐related protein, CHOP/GADD153

• Published in: Journal of neurochemistry 2006-01, Vol.96 (1), p.43-52
• Main Authors: Awai, Maiko, Koga, Takahisa, Inomata, Yasuya, Oyadomari, Seiichi, Gotoh, Tomomi, Mori, Masataka, Tanihara, Hidenobu
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Blotting, Western; Brain research; C/EBP homologous protein; Cell Death - drug effects; endoplasmic reticulum; Endoplasmic Reticulum - metabolism; Excitatory Amino Acid Agonists - toxicity; Eye and associated structures. Visual pathways and centers. Vision; Fundamental and applied biological sciences. Psychology; Heat-Shock Proteins - physiology; Immunohistochemistry; In Situ Nick-End Labeling; Injuries; Injuries of the nervous system and the skull. Diseases due to physical agents; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; N-Methylaspartate - toxicity; NMDA; Proteins; Retina; Retinal Diseases - chemically induced; Retinal Diseases - pathology; retinal ganglion cells; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Rodents; Transcription Factor CHOP - deficiency; Transcription Factor CHOP - genetics; Transcription Factor CHOP - physiology; Traumas. Diseases due to physical agents; Vertebrates: nervous system and sense organs
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2005.03502.x

We investigated the role of an endoplasmic reticulum stress‐associated protein, CHOP/GADD153, after NMDA‐induced mouse retinal damage. After injection of NMDA into the vitreous, TUNEL‐positive cells were detected in the retinal ganglion cell layer (GCL) and inner nuclear layer (INL) at 6 h after NMDA injection, and these gradually increased in number up to 24 h. Analysis by real‐time RT‐PCR revealed that CHOP mRNA was induced by about 3‐fold, at 2 h after NMDA injection. Immunoreactivity for the CHOP protein was intense in cells of the GCL following NMDA treatment. Immunoblot analysis showed that NMDA injection increased the expression of CHOP protein in the retina. Compared with wild‐type mice, CHOP–/– mice were more resistant to NMDA‐induced retinal cell death as determined by TUNEL assay. At 7 days after NMDA treatment, the thickness of the inner plexiform layer and INL were larger in CHOP–/– mice than in wild‐type mice. The number of residual cells in the GCL following NMDA treatment was significantly higher in CHOP–/– mice than in wild‐type mice. In conclusion, CHOP is induced in mouse retina by NMDA treatment, and CHOP–/– mice are more resistant to NMDA‐induced retinal damage, suggesting that CHOP plays an important role in NMDA‐induced retinal cell death.