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Abstract #58952 Published in IGR 16-3
Enhanced survival of retinal ganglion cells is mediated by Müller glial cell-derived PEDF
Unterlauft JD; Claudepierre T; Schmidt M; Müller K; Yafai Y; Wiedemann P; Reichenbach A; Eichler WExperimental Eye Research 2014; 127: 206-214
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 (Müller) 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 Müller glial cells suggesting that glial soluble mediators attenuate the death of RGC. When PEDF was ablated from Müller cells a significantly lower number of RGC survived in RGC-Müller 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 Müller cells, leads to an activation of nuclear factor (NF)-κB in RGC. Furthermore, adding an NF-κB inhibitor (SN50) to PEDF-treated RGC cultures reduced the survival of RGC. These findings strongly suggest that NF-κB activation in RGC is critically involved in the pro-survival action of Müller-cell derived PEDF and plays an important role in maintaining neuronal survival.
Department of Ophthalmology and Eye Hospital, University of Leipzig, Germany. Electronic address: jandarius.unterlauft@medizin.uni-leipzig.de.
Full articleClassification:
3.6 Cellular biology (Part of: 3 Laboratory methods)
11.8 Neuroprotection (Part of: 11 Medical treatment)
3.8 Pharmacology (Part of: 3 Laboratory methods)
