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Y. Munemasa, Y. Kitaoka, N. Piri, J. Caprioli; Modulation of Mitochondrial Function in the Optic Nerve of Rat Glaucoma Model. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4320.
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We investigated the possible mitochondrial membrane permeability and potential in optic nerve and retinal ganglion cell (RGC) after intraocular pressure (IOP) elevation with rat glaucoma model.
Rat glaucoma model was carried out with argon laser photocoagulation after intracameral injection of india ink. 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 levels of thioredoxin2 (Trx2) in RGC and optic nerve were examined with immunoblot analysis. 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.
Elevated IOP was sustained until 5 weeks after laser photocoagulation. Morphometric analysis showed a significant decrease in axon number in glaucomatous eyes. Immunoblot analysis showed a significant decreased mitochondrial Trx2 level, which regulates mitochondrial membrane permeability, in both RGC and optic nerve 5 weeks after IOP elevation. The distribution of dye-labeled mitochondria, which is regulated by mitochondria membrane potential, appeared to be decreased in the lamina cribrosa area 5 weeks after IOP elevation, compared with the contralateral control eye.
These findings provide the possibility that the decreases of mitochondrial membrane permeability and potential are involved in glaucomatous optic neuropathy.
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