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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)-
/ß inducible Mx-promoter (Mx-c-fos), c-fosdeficient 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-fosnull 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-fosmediated cascade involved in RGC apoptosis and regeneration is significant in realizing neuronal survival and regeneration.
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