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(Investigative Ophthalmology and Visual Science. 2002;43:2442-2449.)
© 2002 by The Association for Research in Vision and Ophthalmology, Inc.

The Role of c-fos in Cell Death and Regeneration of Retinal Ganglion Cells

Toshiyuki Oshitari1, Mari Dezawa1,2, Seiji Okada3, Masahiko Takano4, Hisanari Negishi1, Hidenori Horie5, Hajime Sawada2, Takeshi Tokuhisa3 and Emiko Adachi-Usami1

1 From the Departments of Ophthalmology and Visual Science and 3 Developmental Genetics, Graduate School of Medicine, Chiba University, Chiba, Japan; and 2 the Departments of Anatomy, 4 Ophthalmology, and 5 Physiology, Yokohama City, University School of Medicine, Yokohama, Japan.

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)-{alpha} 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.




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