title: Pax6-positive Müller glia cells express cell cycle markers but do not proliferate after photoreceptor injury in the mouse retina.
abstract: In lower vertebrates, such as fish, Müller glia plays an essential role in the restoration of visual function after retinal degeneration by transdifferentiating into photoreceptors and other retinal neurons. During this process, Müller cells re-enter the cell cycle, proliferate, and migrate from the inner nuclear layer (INL) to the photoreceptor layer where they express photoreceptor-specific markers. This process of Müller cell transdifferentiation is absent in mammals, and the loss of photoreceptors leads to permanent vision deficits.The mechanisms underlying the failure of mammalian Müller cells to behave as stem cells after photoreceptor degeneration are poorly understood. In the present study, we show that photoreceptor injury induces migration of PAX6-positive Müller cell nuclei toward the outer part of the INL and into the inner part of the outer nuclear layer. These cells express markers of the cell cycle, suggesting an attempt to re-enter the cell cycle similarly to lower vertebrates.However, mouse Müller cells do not proliferate in response to photoreceptor injury implying a blockade of the S-phase transition. Our results suggest that a release of the S-phase blockade may be crucial for Müller cells to successfully transdifferentiate and replace injured photoreceptors in mammals.
authors.affiliation: Laboratory for Retinal Cell Biology, Department of Ophthalmology, University of Zurich, Switzerland. joly@hifo.uzh.ch
authors.forename: Sandrine
authors.initials: S
authors.lastname: Joly
authors.forename: Vincent
authors.initials: V
authors.lastname: Pernet
authors.forename: Marijana
authors.initials: M
authors.lastname: Samardzija
authors.forename: Christian
authors.initials: C
authors.lastname: Grimm
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D056741:Cyclin D / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D018398:Homeodomain Proteins / Q000378:metabolism*; D008027:Light / Q000009:adverse effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D009154:Mutation / Q000235:genetics; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism*; D010786:Photoreceptor Cells / Q000473:pathology; D012097:Repressor Proteins / Q000378:metabolism*; D012160:Retina / Q000473:pathology*; D012162:Retinal Degeneration / Q000235:genetics / Q000473:pathology; D012164:Retinal Diseases / Q000209:etiology / Q000235:genetics / Q000473:pathology*
chemical_list: D018797:Cell Cycle Proteins; D056741:Cyclin D; D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D001973:Bromodeoxyuridine