Relocalization of apoptosis-inducing factor in photoreceptor apoptosis induced by retinal detachment in vivo

Apoptosis-inducing factor (AIF) is a novel mediator in apoptosis. AIF is a flavoprotein that is normally confined to the mitochondrial intermembrane s pace, yet translocates to the nucleus in several in vitro models of apoptos is. To investigate the role of AIF in the apoptotic process in vivo, we ind uced retinal detachment CRI)) by subretinal injection of sodium hyaluronate , either in Brown Norway rats or in C3H mice. Apoptotic DNA fragmentation, as determined by terminal nick-end labeling, was most prominent 3 days afte r BD, The subcellular localization of AIF was examined by Immunohistochemis try and immunoelectron microscopy, In normal photoreceptor cells, AIF was p resent in the mirtochondrion-rich inner segment. However, AIF was found in the nucleus after RD. Photoreceptor apoptosis developed similarly in C3H co ntrol mice, and in mice bearing the gld or 1pr mutations, indicating that c ell death occurs independently from the CD95/CD95 ligand system. Both the m itochondrio-nuclear transition of AIF localization and the nuclear DNA frag mentation were inhibited by subretinal application of brain-derived neurotr ophic factor. To our knowledge, this is the first description of AIF reloca lization occurring in a clinically relevant, in vivo model of apoptosis.