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Neuropeptide Y-evoked proliferation of retinal glial (Müller) cells

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Abstract

Background

Glial cells in human retinas and in fibrocellular membranes from patients with proliferative vitreoretinopathy (PVR) have been described to upregulate their expression of Y1 receptors for neuropeptide Y (NPY) (Soler et al.: Glia 39:320, 2002). However, it is unknown whether Y1 receptor activation causes proliferation of retinal glial cells. We investigated whether NPY exerts a proliferation-stimulating effect on retinal glial cells, and compared the NPY-evoked signaling with the signaling of purinergic P2Y receptors.

Methods

Proliferation assays using bromodeoxyuridine were carried out on primarily cultured Müller glial cells of the guinea pig, in the absence and presence of blockers of Y1 receptors, of receptor tyrosine kinases (RTKs), of mitogen-activated protein kinases (MAPKs) and of phosphatidylinositol-3 kinase (PI3K).

Results

NPY exerted a biphasic effect on Müller cell proliferation. At low concentrations (0.1 ng/ml and 1 ng/ml) it decreased the proliferation rate of the cells, while at higher concentration (100 ng/ml) it increased Müller cell proliferation. The NPY-evoked proliferation was mediated by Y1 receptor stimulation and by activation of the p44/p42 MAPKs and partially of the p38 MAPK. Moreover, Y1 receptor-induced activation of PI3K as well as transactivations of the platelet-derived and the epidermal growth factor RTKs were necessary for full mitogenic effect of NPY. Y1 and P2Y receptors share partially common signal transduction pathways in Müller cells.

Conclusion

It is suggested that NPY may be involved in stimulation of retinal glial cell proliferation during PVR when it is released at higher amounts into the injured retina.

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Acknowledgements

The authors thank J. Krenzlin for excellent technical assistance. This work was supported in part by a grant from the BMBF (IZKF at the University of Leipzig, 01KS9504, Project C21), and by Grants Re 849/8-3 and Br 1249/2-1 from the DFG.

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Author notes

  1. Ivan Milenkovic

    Present address: Zoological Institute of the University of Leipzig, Talstrasse 33, 04103, Leipzig, Germany

Authors and Affiliations

  1. Paul Flechsig Institute of Brain Research, University of Leipzig, Jahnallee 59, 04109, Leipzig, Germany

    Ivan Milenkovic, Michael Weick & Andreas Reichenbach

  2. Department of Ophthalmology, Eye Clinic, University of Leipzig, Liebigstrasse 10-14, 04103, Leipzig, Germany

    Peter Wiedemann & Andreas Bringmann

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  1. Ivan Milenkovic
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  2. Michael Weick
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  4. Andreas Reichenbach
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  5. Andreas Bringmann
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Correspondence to Andreas Bringmann.

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Milenkovic, I., Weick, M., Wiedemann, P. et al. Neuropeptide Y-evoked proliferation of retinal glial (Müller) cells. Graefe's Arch Clin Exp Ophthalmol 242, 944–950 (2004). https://doi.org/10.1007/s00417-004-0954-3

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  • DOI: https://doi.org/10.1007/s00417-004-0954-3

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