Activation of endoplasmic reticulum stress in degenerating photoreceptors of the rd1 mouse.
OBJECTIVE
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 2alpha (eIF2alpha), 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-eIF2alpha, 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.
Yang
Li-Ping
LP
Peking University Eye Center, Peking University Third Hospital, Peking University, Beijing, PR China. alexlipingyang@gmail.com
Wu
Le-Meng
LM
Guo
Xiu-Juan
XJ
Tso
Mark O M
MO
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D053454:Caspase 12 / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism*; D020287:In Situ Nick-End Labeling; D051379:Mice; D008809:Mice, Inbred C3H; D008856:Microscopy, Fluorescence; D018832:Molecular Chaperones / Q000378:metabolism; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism* / Q000473:pathology; D012162:Retinal Degeneration / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation; D019892:eIF-2 Kinase / Q000378:metabolism
D053454:Caspase 12; D000091342:Endoplasmic Reticulum Chaperone BiP; D015852:Eukaryotic Initiation Factor-2; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D019892:eIF-2 Kinase; C000717248:Hspa5 protein, mouse