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Li-ping Yang, Le-meng Wu, Xiu-juan Guo, Mark O. M. Tso; Activation of Endoplasmic Reticulum Stress in Degenerating Photoreceptors of the rd1 Mouse. Invest. Ophthalmol. Vis. Sci. 2007;48(11):5191-5198. https://doi.org/10.1167/iovs.07-0512.
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purpose. Endoplasmic reticulum (ER) stress has been implicated in a wide variety of neurodegenerative disorders of the central nervous system (CNS). This study was designed to elucidate the role of ER stress in photoreceptor apoptosis in the rd1 mouse.
methods. Photoreceptor apoptosis in the rd1 mouse was detected by terminal dUTP transferase nick-end labeling (TUNEL). Protein expressions of ER stress sensors, including glucose-regulated protein-78 (GRP78/BiP), caspase-12, phospho-eukaryotic initiation factor 2α (eIF2α), and phospho-pancreatic ER kinase (PERK), were examined by immunofluorescence and Western blot assays.
results. Accompanying photoreceptor apoptosis in the rd1 mouse, the protein expressions of GRP78/BiP, caspase-12, phospho-eIF2α, and phospho-PERK were upregulated in a time-dependent manner. The upregulation of these proteins coincided with or preceded photoreceptor apoptosis. At the peak of their expression, these proteins were primarily located in the photoreceptor inner segments, the outer nuclear layer, or both.
conclusions. ER stress plays an important role in photoreceptor apoptosis in the rd1 mouse. Therefore, ER stress modulators may be strong candidates as therapeutic agents in the treatment of retinal degenerative diseases.
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