ER stress and apoptosis: a new mechanism for retinal cell death.
The endoplasmic reticulum (ER) is the primary subcellular organelle where proteins are synthesized and folded. When the homeostasis of the ER is disturbed, unfolded or misfolded proteins accumulate in the ER lumen, resulting in ER stress. In response to ER stress, cells activate a set of tightly controlled regulatory programs, known as the unfolded protein response (UPR), to restore the normal function of the ER. However, if ER stress is sustained and the adaptive UPR fails to eliminate unfolded/misfolded proteins, apoptosis will occur to remove the stressed cells. In recent years, a large body of studies has shown that ER stress-induced apoptosis is implicated in numerous human diseases, such as diabetes and neurogenerative diseases. Moreover, emerging evidence supports a role of ER stress in retinal apoptosis and cell death in blinding disorders such as age-related macular degeneration and diabetic retinopathy. In the present review, we summarize recent progress on ER stress and apoptosis in retinal diseases, focusing on various proapoptotic and antiapoptotic pathways that are activated by the UPR, and discuss how these pathways contribute to ER stress-induced apoptosis in retinal cells.
Department of Medicine, Endocrinology and Diabetes, University of Oklahoma Health Sciences Center, 941 Stanton L. Young Blvd., Oklahoma City, OK 73104, USA.
Guangjun
G
Jing
Joshua J
JJ
Wang
Sarah X
SX
Zhang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D003930:Diabetic Retinopathy / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005136:Eye Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008268:Macular Degeneration / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D058990:Molecular Targeted Therapy; D012160:Retina / Q000187:drug effects / Q000473:pathology*; D012164:Retinal Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D055351:Retinal Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D056811:Unfolded Protein Response / Q000187:drug effects
D005136:Eye Proteins