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 space, yet translocates to the nucleus in several in vitro models of apoptosis. To investigate the role of AIF in the apoptotic process in vivo, we induced retinal detachment (RD) 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 after RD. The subcellular localization of AIF was examined by immunohistochemistry and immunoelectron microscopy. In normal photoreceptor cells, AIF was present in the mitochondrion-rich inner segment. However, AIF was found in the nucleus after RD. Photoreceptor apoptosis developed similarly in C3H control mice, and in mice bearing the gld or lpr mutations, indicating that cell death occurs independently from the CD95/CD95 ligand system. Both the mitochondrio-nuclear transition of AIF localization and the nuclear DNA fragmentation were inhibited by subretinal application of brain-derived neurotrophic factor. To our knowledge, this is the first description of AIF relocalization occurring in a clinically relevant, in vivo model of apoptosis.
Hisatomi
T
T
Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Sakamoto
T
T
Murata
T
T
Yamanaka
I
I
Oshima
Y
Y
Hata
Y
Y
Ishibashi
T
T
Inomata
H
H
Susin
S A
SA
Kroemer
G
G
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051033:Apoptosis Inducing Factor; D003574:Cytochrome c Group / Q000378:metabolism; D053222:Fas Ligand Protein; D005420:Flavoproteins / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D009414:Nerve Growth Factors / Q000502:physiology; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology*; D051381:Rats; D011914:Rats, Inbred BN; D012163:Retinal Detachment / Q000378:metabolism*; D014018:Tissue Distribution; D019014:fas Receptor / Q000502:physiology
C494831:Aifm1 protein, rat; D051033:Apoptosis Inducing Factor; D003574:Cytochrome c Group; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; C505662:Faslg protein, rat; D005420:Flavoproteins; D005904:Glial Fibrillary Acidic Protein; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009414:Nerve Growth Factors; C494830:AIFM1 protein, mouse; D019014:fas Receptor