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Masumi Takeda, Hidemasa Kato, Akira Takamiya, Akitoshi Yoshida, Hiroshi Kiyama; Injury-Specific Expression of Activating Transcription Factor-3 in Retinal Ganglion Cells and Its Colocalized Expression with Phosphorylated c-Jun. Invest. Ophthalmol. Vis. Sci. 2000;41(9):2412-2421.
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© ARVO (1962-2015); The Authors (2016-present)
purpose. To ascribe activating transcription factor (ATF)-3 as a specifically
induced transcription factor after ON injury and to describe its
putative role as a modulator of c-Jun transactivation.
methods. The adult rat optic nerve was crushed intraorbitally, and expression
profiles of ATF-3, ATF-2, and phosphorylated c-Jun (p-c-Jun) were
examined by immunohistochemistry and ISH. Western blot analysis for
ATF-3 and -2 were also performed. Furthermore, colocalized detection of
c-Jun mRNA with ATF-2 or -3 was attempted with a combined method of
simultaneous immunohistochemistry and in situ hybridization.
results. In response to optic nerve injury, substantial expression of ATF-3 as
well as that of p-c-Jun was observed in the retinal ganglion cells,
whereas no expression of ATF-3 was seen in other noninjured retinal
cells. In contrast, ATF-2 was normally expressed abundantly in both
retinal ganglion cells and displaced amacrine cells, but expression
dropped in retinal ganglion cells after nerve injury. The expression
profiles of ATF-2 and -3 after optic nerve injury were confirmed by
Western blot analysis. A higher degree of colocalization was observed
for ATF-3 and c-Jun than the modest codetection for ATF-2 and
conclusions. The transcription factor ATF-3 is specifically induced upon optic nerve
injury and colocalizes with p-c-Jun in surviving ganglion cells. These
findings suggest that both ATF-3 and c-Jun are crucial to trigger
various transcriptional responses and may act synergistically during
the survival phase of the optic nerve in the injury
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