title: Long-term blue light exposure induces RGC-5 cell death in vitro: involvement of mitochondria-dependent apoptosis, oxidative stress, and MAPK signaling pathways.
abstract: The mechanism of blue light-induced retinal ganglion cell (RGC) injury is poorly understood. In this study, we established a patented light-emitting diode-based system to study the effects of long-term blue light exposure under culture conditions on RGC-5 cells. Long-term blue light exposure significantly reduced cell viability in a time-dependent manner and induced apoptosis and necrosis in RGC-5 cells. Long-term blue light exposure marked an increase in the expression of Bax and active Caspase-3 (p17), which was accompanied by Bcl-2 down-regulation, and displayed features of the mitochondria-dependent apoptosis pathway. Blue light exposure also increased the generation of reactive oxygen species (ROS), and was a strong inducer of ROS-sensitive protein nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression. Moreover, blue light exposure constitutively activated p38 mitogen-activated protein kinases and c-Jun NH2-terminal kinase (JNK), as well as induced the phosphorylation of extracellular signal-regulated kinase in the early phase, in blue light-exposed RGC-5 cells. The protein expression of c-jun and c-fos was further enhanced after RGC-5 cells were exposed to blue light. Taken together, these findings indicated that blue light induced RGC-5 cell line death in dependence upon exposure duration. The potential mechanisms for this phenomenon might be via activated mitochondria-dependent apoptosis, increased ROS production and protein expressions of Nrf2 and HO-1, and activated JNK/p38 MAPK signaling pathways.
authors.affiliation: Department of Ophthalmology, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing, 100191, China, candyhuang719@hotmail.com.
authors.forename: Chen
authors.initials: C
authors.lastname: Huang
authors.forename: Pei
authors.initials: P
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Xu
authors.forename: Minshu
authors.initials: M
authors.lastname: Wang
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Chen
authors.forename: Xuran
authors.initials: X
authors.lastname: Dong
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects; D051547:Heme Oxygenase-1 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008027:Light / Q000009:adverse effects*; D020935:MAP Kinase Signaling System; D008928:Mitochondria / Q000378:metabolism / Q000528:radiation effects*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*
chemical_list: D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D051547:Heme Oxygenase-1; D048031:JNK Mitogen-Activated Protein Kinases; D053148:Caspase 3