The role of c-fos in cell death and regeneration of retinal ganglion cells

Toshiyuki Oshitari, Mari Dezawa, Seiji Okada, Masahiko Takano, Hisanari Negishi, Hidenori Horie, Hajime Sawada, Takeshi Tokuhisa, Emiko Adachi-Usami

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)

Abstract

PURPOSE. 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)-α/β 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-tower 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.

Original languageEnglish
Pages (from-to)2442-2449
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume43
Issue number7
Publication statusPublished - 2002 Jul 9
Externally publishedYes

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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