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Abstract #46401 Published in IGR 13-3
Müller Glia: A Promising Target for Therapeutic Regeneration
Ahmad I; Del Debbio CB; Das AV,Parameswaran SInvestigative Ophthalmology and Visual Science 2011; 52: 5758-5764
In the past 10 years, there has been a paradigm shift in our understanding of brain development and approaches to treat degenerative diseases, including those that affect the retina. The latest knowledge includes (1) the discovery that the adult brain harbors proliferating progenitors and that neurons are born throughout life, particularly in the subventricular zone (SVZ) of the lateral ventricle and the subgranular layer (SGL) of the dentate gyrus of the hippocampus1 and (2) the observation that glia perform dual functions, providing homeostatic support and serving as the source of stem cells in the embryonic brain and the adult SVZ and SGL.2 In contrast to the SVZ and SGL, active neurogenesis has not been detected in adult mammalian retina. However, neurogenic changes have been observed in injured retina, and the source of injury-induced neurogenesis is traced to Müller glia, the sole glial cells generated by multipotential retinal progenitors. Recent evidence that a subset of Müller glia possesses an evolutionarily conserved stem cell potential has posited these cells as a viable target for replacing degenerating neurons in diseases such as age-related macular degeneration, retinitis pigmentosa, and glaucoma, where vision loss is due to the degeneration of specific types of neurons. This approach has the potential to effectively address significant barriers, such as the lack of a renewable source of cells that are nonimmunogenic and nonteratogenic, which currently makes ex vivo cell therapy approach impractical. This review describes the recent progress made in our understanding of the stem cell properties and regenerative potential of Müller glia and includes a discussion of (1) the development of Müller glia; (2) the neurogenic potential of Müller glia across species; (3) the characterization of Müller glia as stem cells; (4) the facile activation of Müller glia; and (5) the molecular mechanisms underlying the stemness (i.e., stemlike properties) of Müller glia. This information is critical in making potential therapeutic approaches effective, efficient, predictable, and safe. This review does not include the homeostatic functions of Müller glia; readers are referred to an excellent review on the topic by Bringmann et al.3
Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, NE, USA.
Classification:
11.8 Neuroprotection (Part of: 11 Medical treatment)
