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Cyr61 activates retinal cells and prolongs photoreceptor survival in rd1 mouse model of retinitis pigmentosa.

J. Neurochem. 130, 227-240 (2014)
Open Access Green as soon as Postprint is submitted to ZB.
Subretinal injections with glial cell line-derived neurotrophic factor (GDNF) rescue morphology as well as function of rod cells in mouse and rat animal models of Retinitis pigmentosa. At the same time, it is postulated that this effect is indirect, mediated by activation of retinal Müller glial (RMG) cells. Here we show that Cyr61/CCN1, one of the secreted proteins upregulated in primary RMG after GDNF stimulation, provides neuroprotective and pro-survival capacities: Recombinant Cyr61 significantly reduced photoreceptor cells (PR) death in organotypic cultures of Pde6brd1 retinas. In order to identify stimulated pathways in the retina, we treated Pde6brd1 retinal explants with Cyr61 and observed an overall increase in activated Erk1/2 and Stat3 signalling molecules characterized by activation-site specific phosphorylation. To identify Cyr61 retinal target cells, we isolated primary porcine PR, RMG and retinal pigment epithelium (RPE) cells and exposed them separately to Cyr61. Here, RMG as well as RPE cells responded with induced phosphorylation of Erk1/2, Stat3, and Akt. In PR, no increase in phosphorylation in any of the studied proteins was detected, suggesting an indirect neuroprotective effect of Cyr61. Cyr61 may thus act as an endogenous pro-survival factor for PR, contributing to the complex repertoire of neuroprotective activities generated by RMG and RPE cells.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Neuroprotection ; Retinal Degeneration ; Rmg ; Rpe; Epithelium-derived Factor; Neurotrophic Factor Protects; Oxidative Stress; Rat Model; Muller Cells; Optic-nerve; Phototransduction Machinery; Rod Photoreceptors; Signaling Pathway; Neuroprotectin D1
ISSN (print) / ISBN 0022-3042
e-ISSN 1471-4159
Quellenangaben Volume: 130, Issue: 2, Pages: 227-240 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Hoboken
Reviewing status Peer reviewed