title: Blue Light Action on Mitochondria Leads to Cell Death by Necroptosis.
abstract: Blue light impinging on the many mitochondria associated with retinal ganglion cells (RGCs) in situ has the potential of eliciting necroptosis through an action on RIP1/RIP3 to stimulate RGC death in diseases like glaucoma and diabetic retinopathy. Cells in culture die when exposed to blue light. The death process is mitochondria-dependent and is known to involve a decrease in the production of ATP, a generation of ROS, the activation of poly-(ADP-ribose) polymerase, the stimulation of apoptosis-inducing factor (AIF) as well as the up-regulation of heme-oxygenase-1 (HO-1). Our present results show that blue light-induced activation of AIF is not directly linked with the stimulation of RIP1/RIP3. Down-regulation of RIP1/RIP3 did not influence AIF. AIF activation therefore appears to enhance the rate of necroptosis by a direct action on DNA breakdown, the end stage of necroptosis. This implies that silencing of AIF mRNA may provide a degree of protection to blue light insult. Also, necrostatin-1 attenuated an increased turnover of HO-1 mRNA caused by blue light to suggest an indirect inhibition of necroptosis, caused by the action of necrostatin-1 on RIP1/RIP3 to reduce oxidative stress. This is supported by the finding that gene silencing of RIP1 and RIP3 has no effect on HO-1. We therefore conclude that inhibitors of RIP kinase might be more specific than necrostatin-1 as a neuroprotective agent to blunt solely necroptosis caused by blue light.
authors.affiliation: Fundación de Investigación Oftalmológica, Avda. Doctores Fernández-Vega 34, 33012, Oviedo, Asturias, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Del Olmo-Aguado
authors.affiliation: Fundación de Investigación Oftalmológica, Avda. Doctores Fernández-Vega 34, 33012, Oviedo, Asturias, Spain.
authors.forename: Claudia
authors.initials: C
authors.lastname: Núñez-Álvarez
authors.affiliation: Fundación de Investigación Oftalmológica, Avda. Doctores Fernández-Vega 34, 33012, Oviedo, Asturias, Spain. Neville.osborne@eye.ox.ac.uk.
authors.forename: Neville N
authors.initials: NN
authors.lastname: Osborne
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002470:Cell Survival; D008027:Light; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D009336:Necrosis; D018384:Oxidative Stress / Q000502:physiology; D012165:Retinal Ganglion Cells / Q000378:metabolism; D015854:Up-Regulation
keywords: Apoptosis-inducing factor (AIF); Blue light; Heme-oxygenase-1 (HO-1); Mitochondria; Necroptosis; Protein kinase-1 (RIP1) and 3 (RIP3)