Cellular signaling and factors involved in Muller cell gliosis: Neuroprotective and detrimental effects

Muller cells are active players in normal retinal function and in virtually all forms of retinal injury and disease. Reactive Willer cells protect the tissue from further damage and preserve tissue function by the release of antioxidants and neurotrophic factors, and may contribute to retinal regeneration by the generation of neural progenitor/stem cells. However, Muller cell gliosis can also contribute to neurodegeneration and impedes regenerative processes in the retinal tissue by the formation of glial scars. This article provides an overview of the neuroprotective and detrimental effects of Muller cell gliosis, with accounts on the cellular signal transduction mechanisms and factors which are implicated in Muller cell-mediated neuroprotection, immunomodulation, regulation of Muller cell proliferation, upregulation of intermediate filaments,glial scar formation, and the generation of neural progenitor/stem cells. A proper understanding of the signaling mechanisms implicated in gliotic alterations of Muller cells is essential for the development of efficient therapeutic strategies that increase the supportive/protective and decrease the destructive roles of gliosis. (C) 2009 Elsevier Ltd. All rights reserved.