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N. Rodriguez-Muela, F. Germain, P. Boya; Activation of Autophagy After Optic Nerve Transection. Invest. Ophthalmol. Vis. Sci. 2009;50(13):149.
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Autophagy is an intracellular pathway by which cells degrade and recycle macromolecules. It is a homeostatic process necessary for the clearance of damaged or superfluous proteins and organelles. In addition, the recycling of intracellular constituents also provides energy during periods of metabolic stress, thereby contributing to cell viability. By contrast, autophagy may have a role in several pathogenic conditions such as during neurodegenerative diseases. Optic nerve axotomy is a traumatic model of central nervous system degeneration, which induces death of retinal ganglion cell (RGC) that has been widely used in rabbits and rats.
In the present work we have studied optic nerve axotomy in the GFP-LC3 mice, a mouse model that allows the determination of autophagy in vivo and determined the kinetics of cell death and autophagy activation after optic nerve axotomy. RGCs loss was studied up to one month after optic nerve transection by immunohistochemistry and retrograde labeling. Cell death was determined with a commercial ELISA kit and active caspase-3 analysis. Autophagy induction was assessed by western-blot, q-RT-PCR, confocal and electron microscopy.
Our data show that the peak of RGC death occurs around day 6 post-axotomy, and leads to a reduction in RGC numbers determined by Brain-3 and retrograde DMTR labeling in flat-mounted retinas. Moreover we find an increase in autophagy by confocal microscopy and distinct biochemical tecniques, at day 3 post-axotomy. Ultrastructural analyses confirmed autophagosomes in the cytosol of affected neurons.
These data indicate that autophagy is activated in RGC shortly after optic nerve axotomy and before the peak of cell death. We are currently investigating whether this activation may act as a pro-survival mechanism or in the contrary plays a role in the execution of cell death.
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