Control of Müller glial cell proliferation and activation following retinal injury.
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.
Dyer
M A
MA
Department of Genetics and Howard Hughes Medical Institute, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA.
Cepko
C L
CL
D000818:Animals; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000502:physiology*; D002478:Cells, Cultured; D056743:Cyclin D3; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015536:Down-Regulation / Q000502:physiology; D005911:Gliosis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000172:deficiency* / Q000235:genetics; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D012160:Retina / Q000293:injuries / Q000473:pathology* / Q000503:physiopathology*; D012161:Retinal Artery / Q000473:pathology / Q000503:physiopathology; D015792:Retinal Dysplasia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D025521:Tumor Suppressor Proteins; D015854:Up-Regulation / Q000502:physiology
C534697:Ccnd3 protein, mouse; C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D056743:Cyclin D3; D016213:Cyclins; D008869:Microtubule-Associated Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27