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Y. Munemasa, Y. Kitaoka, J. Kuribayashi, Y. Hayashi, H. Takeda, S. Ueno; Modulation of Axonal Transport of Mitochondria in Rat Glaucoma Model. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2114.
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© ARVO (1962-2015); The Authors (2016-present)
Modulation of anterograde and retrograde axonal transport of mitochondria is important to understand the mechanism of axonal degeneration and subsequent retinal ganglion cell (RGC) death. We investigate the changes in mitochondria-related axonal motor proteins, and behaviour of mitochondria in glaucomatous optic neuropathy.
Rat glaucoma model was carried out with argon laser photocoagulation. Dark-phase IOP measurements were monitored with a portable tonometer (Tonolab). RGC isolation was performed with magnetic beads coated with Thy-1 monoclonal antibody. The changes in mitochondria-related axonal motor proteins, such as kinesin-1 and myosin, in the optic nerve and RGC were examined with immunoblot analysis. The translocation of apoptosis-inducing factor (AIF), which is mitochondria-related cell death molecular, from the axon to nucleus of cell body was studied with immunoblot and immunohistochemistry. At 5 weeks after IOP elevation, retrograde labeling to identify mitochondria was performed by placing a gelfoam soaked with MitoTracker Red CMXRos to the superior colliculus 1 week before the enucleation. The distribution of mitochondria was examined with fluorescence confocal microscope.
Immunoblot analysis showed a significant decrease in kinesin-1 and myosin, which regulate axonal transport of mitochondria, in the optic nerve 2 weeks after IOP elevation. An increase in AIF level was observed in the nucleus fraction of RGC at 5 weeks after IOP elevation, compared with the control. The translocation of AIF from mitochondria to nucleus was confirmed with immunohistochemistry. Dye-labeled mitochondria appeared to be decreased in the lamina area 5 weeks after IOP elevation, compared with COX4 immunoreactivities.
These findings provide the possibility that the decreases in axonal transport of mitochondria and AIF translocation are involved in glaucomatous optic neuropathy and RGC death.
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