Modulation of mitochondria in the axon and soma of retinal ganglion cells in a rat glaucoma model.
Mitochondrial abnormality has been implicated in various models of retinal ganglion cell (RGC) degeneration. We investigated modulation of mitochondrial membrane permeability and apoptosis-inducing factor (AIF) translocation in a rat experimental glaucoma model. A decrease in MitoTracker-labeled mitochondria around the lamina area of the optic nerve was observed in the glaucomatous eye. Immunoblot analysis for axonal motor proteins showed that a significant decrease in kinesin 1 and myosin Va levels in the glaucomatous optic nerve. A significant decrease in mitochondrial thioredoxin 2 (Trx2) level was observed in the optic nerve after intraocular pressure (IOP) elevation. Translocation of AIF from the mitochondria to the axoplasm and nucleus was observed in the axon and cell body, respectively. Trx2 over-expression in the mitochondrial membrane of RGC-5 cells inhibited AIF translocation, resulting in cytoprotective effect against neurotoxicity induced by TNF-α/buthionine sulfoximine treatment. In vivo transfection was performed with EGFP-Trx2 plasmid and electroporation. Over-expression of Trx2 in the retina and optic nerve indicated the protective effect against high IOP induced axonal degeneration. Thus, the decreased mitochondrial membrane potential and subsequent AIF translocation were involved in the glaucomatous neurodegeneration. Furthermore, modulation of mitochondria through the inhibition of AIF translocation may become a new treatment strategy for neurodegenerative disease, such as glaucoma.
Department Ophthalmology, St Marianna University School of Medicine, Kawasaki, Japan. munemasa@marianna-u.ac.jp
Yasunari
Y
Munemasa
Yasushi
Y
Kitaoka
Junko
J
Kuribayashi
Satoki
S
Ueno
D000818:Animals; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005901:Glaucoma / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008928:Mitochondria / Q000473:pathology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012165:Retinal Ganglion Cells / Q000378:metabolism* / Q000473:pathology
D051033:Apoptosis Inducing Factor