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(Investigative Ophthalmology and Visual Science. 2000;41:2412-2421.)
© 2000 by The Association for Research in Vision and Ophthalmology, Inc.

Injury-Specific Expression of Activating Transcription Factor-3 in Retinal Ganglion Cells and Its Colocalized Expression with Phosphorylated c-Jun

Masumi Takeda1,2, Hidemasa Kato1, Akira Takamiya1,2, Akitoshi Yoshida2 and Hiroshi Kiyama1

From the Departments of 1 Anatomy and 2 Ophthalmology, Asahikawa Medical College, Asahikawa, Japan.

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 c-Jun.

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 model.




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