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B. Beirowski, E. Babetto, M. P. Coleman, K. R. Martin; Differential Effects of the Slow Wallerian Degeneration Gene (WLDS) on Protection of Retinal Ganglion Cell Compartments Following Focal Optic Nerve Injury and Experimental Glaucoma. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5060.
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The pathways leading to retinal ganglion cell (RGC) degeneration in glaucoma are elusive. There are conflicting reports about whether the WldS gene is able to protect RGCs in their entirety following optic nerve (ON) injury in mice. We tested if transgenic expression of WldS in rats protected individual RGC compartments from degeneration following different focal ON injuries and induction of experimental glaucoma.
Adult WldS transgenics and age matched wild-type (WT) rats underwent unilateral optic nerve transection or crush 2-3mm from the globe, or induction of experimental glaucoma by laser photocoagulation of the trabecular meshwork. Detailed quantification of axonal survival was performed in semithin optic nerve cross-sections from both proximal and distal ON segments (ca 5mm and 15mm from globe). RGC body survival was quantified in retinal wholemounts labelled with α - Neuronal Class III β-tubulin (TUJ1) and α - NeuN antibodies.
WldS markedly delayed RGC axonal degeneration 7 and 14 days after surgical ON lesion. After 2 weeks of glaucoma, axonal survival was significantly greater in WldS compared to WT rats exclusively in proximal ON segments (p < 0.00005). Axonal protection was undetectable four weeks after glaucoma induction in WldS transgenics. Interestingly, optic axonal degeneration followed a proximodistal trend both after surgical lesion and glaucoma induction. Despite temporary axonal protection, WldS did not delay RGC somatic degeneration in any lesion paradigm applied.
RGC somatic and axonal degeneration occur by different pathways following either surgical ON lesion or experimental glaucoma in the rat. The axonal degeneration pathway can be temporarily blocked by WldS expression, but the WldS phenotype does not appear to protect against RGC somal degeneration. WldS rats provide a unique tool to assess the significance of axonal neuroprotection in a rat glaucoma model.
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