Endoplasmic reticulum stress is activated in light-induced retinal degeneration.
Exposure to excessive levels of light induces photoreceptor apoptosis and has previously been used as a model for the study of retinal degeneration. During the light exposure, intracellular calcium levels increase, and reactive oxygen species (ROS) are generated, which have been shown to cause endoplasmic reticulum (ER) stress. In the present study, we investigated the role of ER stress in light-induced photoreceptor apoptosis. Our study demonstrated that, after light exposure, the ER stress sensors including glucose-regulated protein-78 (GRP78/BiP), caspase-12, phospho-eukaryotic initiation factor 2 alpha (eIF2 alpha), and phospho-pancreatic ER kinase (PERK) were significantly up-regulated in a time-dependent manner. The up-regulation of these proteins coincided with or preceded the photoreceptor apoptosis indicated by TUNEL. These data showed that ER stress played an important role in light-induced photoreceptor apoptosis. Therefore, ER stress modulators could 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, People's Republic of China. alexlipingyang@gmail.com
Wu
Le-meng
LM
Guo
Xiu-juan
XJ
Li
Ying
Y
Tso
Mark O M
MO
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000473:pathology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D020287:In Situ Nick-End Labeling; D008027:Light / Q000009:adverse effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism / Q000473:pathology*; D012160:Retina / Q000473:pathology; D012162:Retinal Degeneration / Q000378:metabolism / Q000473:pathology*