Turning Muller Glia into Neural Progenitors in the Retina

Stimulating neuronal regeneration is a potential strategy to treat sight-threatening diseases of the retina. In some classes of vertebrates, retinal regeneration occurs spontaneously to effectively replace neurons lost to acute damage in order to restore visual function. There are different mechanisms and cellular sources of retinal regeneration in different species, include the retinal pigmented epithelium, progenitors seeded across the retina, and the Muller glia. This review briefly summarizes the different mechanisms of retinal regeneration in frogs, fish, chicks, and rodents. The bulk of this review summarizes and discusses recent findings regarding regeneration from Muller glia-derived progenitors, with emphasis on findings in the chick retina. The Muller glia are a promising source of regeneration-supporting cells that are intrinsic to the retina and significant evidence indicated these glias can be stimulated to produce neurons in different classes of vertebrates. The key to harnessing the neurogenic potential of Muller glia is to identify the secreted factors, signaling pathways, and transcription factors that enable de-differentiation, proliferation, and neurogenesis. We review findings regarding the roles of mitogen-activated protein kinase and notch signaling in the proliferation and generation of Muller glia-derived retinal progenitors.