Abstract
Müller glial cells are the major support cell for neurons in the vertebrate retina. Following neuronal damage, Müller cells undergo reactive gliosis, which is characterized by proliferation and changes in gene expression. We have found that downregulation of the tumor supressor protein p27Kip1 and re-entry into the cell cycle occurs within the first 24 hours after retinal injury. Shortly thereafter, Müller glial cells upregulate genes typical of gliosis and then downregulate cyclin D3, in concert with an exit from mitosis. Mice lacking p27Kip1 showed a constitutive form of reactive gliosis, which leads to retinal dysplasia and vascular abnormalities reminiscent of diabetic retinopathy. We conclude that p27Kip1 regulates Müller glial cell proliferation during reactive gliosis.
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Acknowledgements
We thank M.H. Baron for discussion and support throughout this project, S. Elledge, W. Harper and P. Zhang for cDNAs; J. Roberts and L.H. Tsai for knockout mice, and J. Zitz, M. Peters and L. Rose for technical support. M.A. Dyer was supported by NRSA fellowship # EY06803-02 and the Charles H. Revson Foundation Fellowship for Biomedical Research. This work was supported by National Institutes of Health Grant # EY0-8064.
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Dyer, M., Cepko, C. Control of Müller glial cell proliferation and activation following retinal injury. Nat Neurosci 3, 873–880 (2000). https://doi.org/10.1038/78774
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DOI: https://doi.org/10.1038/78774
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