NMDA-induced retinal injury is mediated by an endoplasmic reticulum stress-related protein, CHOP/GADD153.
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.
Awai
Maiko
M
Department of Ophthalmology and Visual Science, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
Koga
Takahisa
T
Inomata
Yasuya
Y
Oyadomari
Seiichi
S
Gotoh
Tomomi
T
Mori
Masataka
M
Tanihara
Hidenobu
H
D000818:Animals; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D006360:Heat-Shock Proteins / Q000502:physiology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016202:N-Methylaspartate / Q000633:toxicity*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012164:Retinal Diseases / Q000139:chemically induced* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051742:Transcription Factor CHOP / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
C497250:Ddit3 protein, mouse; D018690:Excitatory Amino Acid Agonists; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D051742:Transcription Factor CHOP; D016202:N-Methylaspartate