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Involvement of endoplasmic reticulum stress in optic nerve degeneration following N ‐methyl‐ D ‐aspartate‐induced retinal damage in mice
Author(s) -
Shimazawa Masamitsu,
Miwa Akinori,
Ito Yasushi,
Tsuruma Kazuhiro,
Aihara Makoto,
Hara Hideaki
Publication year - 2012
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.23078
Subject(s) - optic nerve , nmda receptor , retinal ganglion cell , endoplasmic reticulum , retinal degeneration , microbiology and biotechnology , glial fibrillary acidic protein , retina , chemistry , biology , neuroscience , receptor , immunology , biochemistry , immunohistochemistry
We evaluated time‐dependent optic nerve degeneration and the role of endoplasmic reticulum (ER) stress in this process following retinal ganglion cell death in mice. Retinal damage was induced by intravitreal injection of N ‐methyl‐ D ‐aspartate (NMDA). Neurofilament heavy (NFH)‐ and phosphorylated NFH (pNFH)‐positive axons were time‐dependently decreased in optic nerves at 1, 3, 7, 14, and 28 days after NMDA injection. Expression of glial fibrillary acidic protein (GFAP)‐positive astroglial cells and ionized calcium‐binding adaptor molecule 1 (Iba1)‐positive microglial cells showed a significant increase in the optic nerve at 7, 14, and 28 days after NMDA injection. In contrast, expression of myelin basic protein (MBP)‐positive oligodendrocytes showed a significant decrease in the optic nerve at 7, 14, and 28 days after NMDA injection. In quantitative RT‐PCR analysis, expressions of glucose‐regulated protein 78 ( Grp78 )/BiP, Grp94 , Calreticulin , C/EBP homologous protein ( Chop ), and the ER degradation enhancer mannosidase alpha‐like 1 ( Edem1 ) genes were increased in the optic nerve at 14 days after NMDA injection. In addition, the Grp94 gene was increased at 7 days after NMDA injection, and the Edem1 gene was increased at 3, 7, and 28 days after NMDA injection. GRP78 and CHOP proteins were colocalized with MBP in the optic nerve after NMDA injection. These findings suggest that the axonal degeneration is dramatic until 7 days after NMDA injection and that glial cells may play some role in the degeneration of the optic nerve. Furthermore, ER stress may play a pivotal role in the decrease of MBP‐positive oligodendrocytes after NMDA‐induced retinal damage. © 2012 Wiley Periodicals, Inc.