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P. P. Monnier, P. Koeberle; RGMa Promotes Retinal Ganglion Cell Survival After Optic Nerve Transection. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5548.
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Recently, we demonstrated that RGMa and Neogenin regulate neuronal cell death in the Central Nervous System. Neogenin induces cell death in the absence of RGMa, whereas association with RGMa promotes survival. Neogenin pro-apoptotic activity in neuronal cells is associated with the activation of capase3. Caspase 3 is implicated in cell death due to Neogenin and to Glaucoma. Neogenin is expressed at the surface of RGC in the eye of adult rats. Based on these observations we hypothesized that Neogenin is involved in RGC death in glaucoma. To address this hypothesis, we studied the effects of RGMa on RGC survival both in vitro and in vivo.
To study the role of RGMa on RGC we developed an in vitro model in which retinal whole mounts are prepared. RGMa or a control protein were added directly to the medium and the preparations placed in an incubator. Four days after preparation, cell death was accessed by performing a propidium iodide staining.For the in vivo study, we used a model of optic nerve transection in rat. Directly after transection, RGMa was injected in the vitreous of the eye. A retrograde staining allowed to visualize RGC that survive 14 days after injury.
In vitro, presence of RGMa promotes RGC survival up to 30% when compared to control pretein.In vivo, RGC survival was enhanced up to five times in RGMa injected eyes when compared to control eyes.
Our data show that RGMa strongly promotes RGC survival in whole mount preparations as well as after optic nerve transection, a well established model for glaucoma. This represents the first evidence for an involvement of RGMa and its receptor, the transmembrane protein Neogenin, in Glaucoma pathology.This set of experiments is important because it will characterize a novel pathway to enhance RGC survival after optic nerve transection. This may offer a means to foster RGC survival in Glaucoma pathology.
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