Control of Muller glial cell proliferation and activation following retinal injury

Muller glial cells are the major support cell for neurons in the vertebrate retina. Following neuronal damage, Muller cells undergo reactive gliosis, which is characterized by proliferation and changes in gene expression. We have found that downregulation of the tumor supressor protein p27(Kip1) and entry into the cell cycle occurs within the first 24 hours after retinal i njury. Shortly thereafter, Muller glial cells upregulate genes typical of g liosis and then downregulate cyclin D3, in concert with an exit from mitosi s. Mice lacking p27(Kip1) showed a constitutive form of reactive gliosis, w hich leads to retinal dysplasia and vascular abnormalities reminiscent of d iabetic retinopathy. We conclude that p27(Kip1) regulates Muller glial cell proliferation during reactive gliosis.