Muller glial cells are the major support cell for neurons in thevertebrate retina. Following neuronal damage, Muller cells
undergoreactive gliosis, which is characterized by proliferation and changesin gene expression. We have found that downregulation of the tumorsupressor protein p27Kip1 and re-entry into the cell cycle occurswithin the first 24 hours after retinal injury. Shortly thereafter,Muller glial cells upregulate genes typical of gliosis and thendownregulate cyclin D3, in concert with an exit from mitosis. Micelacking p27Kip1 showed a constitutive form of reactive gliosis, whichleads to retinal dysplasia and vascular abnormalities reminiscent ofdiabetic retinopathy. We conclude that p27Kip1 regulates Muller glialcell proliferation during reactive gliosis.In recent years, researchinterest in astrocytes and oligodendrocytes, the glial cells of the centralnervous system, has increased markedly. Several studies have describedextensive glial cell
pathology in CNS degenerative diseases. This work is ofspecial interest to researchers of Alzheimer's disease and otherneurodegenerative
disorders because some of the pathology involves tau protein.As yet, however, scientists have not determined whether the glial celldisorders are part of the process of neurodegenerative disorders or are purelya secondary effect of the diseases. Tthese abnormalities inglial cells are not purely secondary to neuronal degeneration," says Dr.James Goldman, professor of pathology and director of the division ofneuropathology. "There are specific glial pathologies in neurologicaldiseases that are similar to what you see in neurons in some of those samediseases. Furthermore, these glial changes differ from those produced bystroke, demyelinating diseases, trauma, or infection." Along with Dr. Steven Chin,assistant professor of pathology, Dr. Goldman researches the changes that occurin glial cells during such neurodegenerative disorders as Alzheimer's disease,progressive supranuclear palsy, cortico-basal ganglionic degeneration, andmulti-system atrophy. These changes surprised researchers when they were firstdiscovered because until then, studies had focused on neurons, not glia. But,says Dr. Goldman, glia are easier to grow in culture; it is even possible togrow glial cells from brain specimens of patients with neurodegenerativedisorders, bringing up many experimental possibilities. If glial changes are infact due to a primary deficit in the disorder, studying living glial cells maygive insights into the metabolism and pathology of the disorder that can't begained from simply studying a slice of the brain. For example, researcherscould use human glial cells to study abnormal metabolic processing of tau.