CaMK II -induced Drp1 phosphorylation contributes to blue light-induced AIF-mediated necroptosis in retinal R28 cells.

Retinal damage caused by blue light has become an important public health concern. Mitochondria have been found to play a key role in light-induced retinal cell death. In this study, we aimed to clarify the molecular mechanism involved in mitochondrion-related retinal cell damage caused by blue light, the major component of light-emitting diodes (LEDs). Our results show that blue light (450 nm, 300lux)-induced R28 cell death is caspase independent and can be attenuated by necrostatin-1. Apoptosis-inducing factor (AIF) cleavage and translocation to the nucleus are involved in the cell death progress. Blue light exposure causes mitochondrial fragmentation, which is mediated by phosphorylation at dynamin-related protein 1 (Drp1) Ser616 site, but it does not alter the protein levels of fission or fusion machinery. Knocking down Drp1 or treatment with Drp1 inhibitor Mdivi-1 protects R28 cells from blue light. Overproduction of reactive oxygen species (ROS) is induced by blue light. The ROS scavenger Trolox decreases Drp1 Ser616 phosphorylation level and mitochondrial fragmentation upon blue light exposure. Moreover, Calcium/calmodulin-dependent protein kinase II (CaMKII) inhibitor KN93 blocks Drp1 phosphorylation and rescues mitochondrial fragmentation and AIF-mediated cell death caused by blue light. In conclusion, our data suggest that the CaMKII-Drp1 pathway plays a major role in blue light-induced AIF-mediated retinal cell damage.