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S. Suemori, M. Shimazawa, T. Yamamoto, H. Hara; Involvement of Endoplasmic Reticulum Stress in Retinal Cell Death. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2499.
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To clarify whether endoplasmic reticulum (ER) stress involved in retinal cell death using cultured retinal ganglion cells (RGC-5, a rat ganglion cell line transformed with E1A virus) in vitro and mice in vivo.
RGC-5 damage was induced by tunicamycin at 1, 2 and 4 µg/ml, and cell viability was measured by Hoechst 33342 and YO-PRO-1 or propidium iodide double nuclear stainings. The expressions of glucose-regulated protein 78(GRP78)/BiP, the phosphorylated form of eukaryotic initiation factor 2α (p-eIF2α), and C/EBP-homologous (CHOP) protein after tunicamycin at 2 µg/ml (in vitro and in vivo) were measured using immunoblot. To induce ER stress in vivo, tunicamycin at 0.1 and 1 µg was intravitreously administered in mice. Seven days after the injection, cell number in ganglion cell layer (GCL) and thickness of inner plexiform layer (IPL) were evaluated.
Treatment with tunicamycin induced apoptotic cell death in RGC-5. GRP78/BiP, a biomarker of ER stress, increased time-dependently throughout the 24 h tunicamycin treatment period. Treatment with tunicamycin time-dependently induced eIF2α phosphorylation, while total eIF2α levels were not changed during the 24-h observation period. CHOP was first detected at 6 h after addition of tunicamycin and persisted thereafter. In vivo, intravitreal injection of tunicamycin at 0.1 µg/eye (a low dose) induced a significant loss of cells in the GCL, but no thinning of the IPL. At a high dose of 1µg/eye, tunicamycin significantly decreased both the cell count in GCL and IPL thickness.
These data indicate that ER stress may play a pivotal role in retinal cell death.
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