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Enhanced survival of retinal ganglion cells is mediated by Muller glial cell-derived PEDF

Abstract : The death of retinal ganglion cells (RGC) leads to visual impairment and blindness in ocular neurodegenerative diseases, primarily in glaucoma and diabetic retinopathy; hence, mechanisms that contribute to protecting RGC from ischemia/hypoxia are of great interest. We here address the role of retinal glial (Muller) cells and of pigment-epithelium-derived factor (PEDF), one of the main neuroprotectants released from the glial cells. We show that the hypoxia-induced loss in the viability of cultured purified RGC is due to apoptosis, but that the number of viable RGC increases when co-cultured with Muller glial cells suggesting that glial soluble mediators attenuate the death of RGC. When PEDF was ablated from Muller cells a significantly lower number of RGC survived in RGC-Muller cell co-cultures indicating that PEDF is a major survival factor allowing RGC to escape cell death. We further found that RGC express a PEDF receptor known as patatin-like phospholipase domain-containing protein 2 (PNPLA2) and that PEDF exposure, as well as the presence of Muller cells, leads to an activation of nuclear factor (NF)-kappa B in RGC. Furthermore, adding an NF-kappa B inhibitor (SN50) to PEDF-treated RGC cultures reduced the survival of RGC. These findings strongly suggest that NF-kappa B activation in RGC is critically involved in the pro-survival action of Muller-cell derived PEDF and plays an important role in maintaining neuronal survival.
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Submitted on : Thursday, July 13, 2017 - 3:26:05 PM
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Jan Darius Unterlauft, Thomas Claudepierre, Manuela Schmidt, Katja Mueller, Yousef Yafai, et al.. Enhanced survival of retinal ganglion cells is mediated by Muller glial cell-derived PEDF. Experimental Eye Research, 2014, 127, pp.206-214. ⟨10.1016/j.exer.2014.08.004⟩. ⟨hal-01562068⟩



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