title: The role of c-fos in cell death and regeneration of retinal ganglion cells.
abstract: OBJECTIVE
  To investigate the effect of c-fos on apoptotic cell death and regeneration of damaged retinal ganglion cells (RGCs) in tissue culture of retinal explants.
  
  
  METHODS
  Retinas from transgenic mice carrying the exogenous c-fos gene under the control of the interferon (IFN)-alpha/beta inducible Mx-promoter (Mx-c-fos), c-fos-deficient mice, and littermate control mice were dissected and cultured in a three-dimensional collagen gel culture system, followed by an analysis of TdT-dUTP terminal nick-end labeling (TUNEL) staining and measurement of neurites that emerged from explants.
  
  
  RESULTS
  Compared with littermate control mice, Mx-c-fos transgenic animals showed a higher ratio of TUNEL positivity in the RGC layer from early in the culture period that correlated with the small number of regenerating neurites. In contrast, the c-fos-null mutated mice showed a still-lower ratio of TUNEL-positive cells. Nevertheless, the number of regenerating neurites was significantly lower in the initial phase, although the drastic increase in density of neurite regeneration was observed in the late period of culture.
  
  
  CONCLUSIONS
  These findings suggest that c-fos is involved in both apoptotic cell death and regeneration of damaged RGCs. Elucidation of the precise c-fos-mediated cascade involved in RGC apoptosis and regeneration is significant in realizing neuronal survival and regeneration.
authors.affiliation: Department of Ophthalmology and Visual Science, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Oshitari
authors.forename: Mari
authors.initials: M
authors.lastname: Dezawa
authors.forename: Seiji
authors.initials: S
authors.lastname: Okada
authors.forename: Masahiko
authors.initials: M
authors.lastname: Takano
authors.forename: Hisanari
authors.initials: H
authors.lastname: Negishi
authors.forename: Hidenori
authors.initials: H
authors.lastname: Horie
authors.forename: Hajime
authors.initials: H
authors.lastname: Sawada
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tokuhisa
authors.forename: Emiko
authors.initials: E
authors.lastname: Adachi-Usami
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D016762:Genes, fos / Q000502:physiology*; D020287:In Situ Nick-End Labeling; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D009416:Nerve Regeneration / Q000502:physiology*; D016501:Neurites / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000502:physiology*; D051020:bcl-X Protein
chemical_list: C494812:Bcl2l1 protein, mouse; D008565:Membrane Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016760:Proto-Oncogene Proteins c-fos; D051020:bcl-X Protein