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NMDA‐induced retinal injury is mediated by an endoplasmic reticulum stress‐related protein, CHOP/GADD153
Author(s) -
Awai Maiko,
Koga Takahisa,
Inomata Yasuya,
Oyadomari Seiichi,
Gotoh Tomomi,
Mori Masataka,
Tanihara Hidenobu
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03502.x
Subject(s) - chop , inner plexiform layer , retina , ganglion cell layer , retinal ganglion cell , nmda receptor , tunel assay , inner nuclear layer , endoplasmic reticulum , biology , retinal , microbiology and biotechnology , endocrinology , apoptosis , chemistry , medicine , neuroscience , biochemistry , receptor
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.