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Identification of a novel neurotrophic factor from primary retinal Müller cells using SILAC.

Mol. Cell. Proteomics 13, 2371-2381 (2014)
Open Access Green as soon as Postprint is submitted to ZB.
Retinal Muller glial cells (RMG) have a primary role in maintaining the homeostasis of the retina. In pathological situations, RMG execute protective and regenerative effects, but can also contribute to neurodegeneration. Cultured primary RMG have recently been recognized to secrete pro-survival factors for retinal neurons for up to two weeks in culture, but this ability is lost when RMG are cultivated for longer durations. In our study, we investigated RMG supernatants for novel neuroprotective factors using a quantitative proteomic approach. Stable isotope labeling by amino acids in cell culture (SILAC) was used on primary porcine RMG. Supernatants of RMG cultivated for two weeks were compared to supernatants from cells which had already lost their protective capacity. Using this approach, we detected established neurotrophic factors such as transferrin, osteopontin (SPP1), and leukemia inhibitory factor (LIF), and identified C-X-C motif chemokine 10 (CXCL10) as a novel candidate neuroprotective factor. All factors prolonged photoreceptor survival in vitro. Ex-vivo treatment of retinal explants with LIF or CXCL10 demonstrated a neuroprotective effect on photoreceptors (PR). Western blots on CXCL10 and LIF stimulated explanted retina and PR lysates indicated activation of pro-survival Signal Transducer and Activator of Transcription (STAT) signaling and B-cell lymphoma (BCL) pathways. These findings suggest that CXCL10 contributes to the supportive potential of RMG towards retinal neurons.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Cxcl10 ; Neurodegenerative Diseases* ; Quantification ; Silac ; Stat Signaling ; Secretome ; Tandem Mass Spectrometry ; Neuroprotection ; Photoreceptor Survival ; Retinal Explants; Leukemia Inhibitory Factor; Optic-nerve; Glial-cells; Pigmented Epithelium; Diabetic-retinopathy; Conditioned Medium; Oxidative Injury; Iron Homeostasis; Primary Neurons; Ganglion-cells
ISSN (print) / ISBN 1535-9476
e-ISSN 1535-9484
Quellenangaben Volume: 13, Issue: 9, Pages: 2371-2381 Article Number: , Supplement: ,
Publisher American Society for Biochemistry and Molecular Biology
Publishing Place Bethesda
Reviewing status Peer reviewed