May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Phosphorylation of CREB and Up-Regulation of BDNF in TNF--Induced Optic Nerve Degeneration
Author Affiliations & Notes
  • H. Fujino
    Ophthalmology, St. Marianna Univ Sch of Med, Kawasaki, Japan
  • Y. Kitaoka
    Ophthalmology, St. Marianna Univ Sch of Med, Kawasaki, Japan
  • H. Takeda
    Ophthalmology, St. Marianna Univ Sch of Med, Kawasaki, Japan
  • Y. Hayashi
    Ophthalmology, Shinkawabashi Hospital, Kawasaki, Japan
  • Y. Munemasa
    Ophthalmology, Jules Stein Eye Institute/UCLA, Los Angeles, California
  • S. Ueno
    Ophthalmology, St. Marianna Univ Sch of Med, Kawasaki, Japan
  • Footnotes
    Commercial Relationships  H. Fujino, None; Y. Kitaoka, None; H. Takeda, None; Y. Hayashi, None; Y. Munemasa, None; S. Ueno, None.
  • Footnotes
    Support  Grants-in-aid for scientific research of Japanese Ministry of Education, Culture, Sports, Science and Technology (No. 18791303)
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 4937. doi:https://doi.org/
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    • Get Citation

      H. Fujino, Y. Kitaoka, H. Takeda, Y. Hayashi, Y. Munemasa, S. Ueno; Phosphorylation of CREB and Up-Regulation of BDNF in TNF--Induced Optic Nerve Degeneration. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4937. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Brain-derived neurotrophic factor (BDNF), a member of the potent survival and developmental factors whose expression is regulated by cyclic AMP-response element binding protein (CREB). Several reports indicate that BDNF prevents retinal ganglion cell body death. The purpose of the present study is to investigate whether BDNF has a neuroprotective effect on their axon in TNF-α-induced optic nerve degeneration.

Methods: : Eight-week-old Wistar rats were received intravitreal injection of 10 ng TNF-α, and 0.1 or 1 µg BDNF simultaneously into one eye. PBS was administered as a control. Eyes were obtained from animals 1 day, 1 or 2 weeks after intravitreal injection. The acquired images of cross-sections of optic nerves were quantified on computer. The protein levels of p-CREB in the retina and the optic nerve were examined by Western blot analysis. Localization of p-CREB was detected by immunohistochemistry. BDNF mRNA in the optic nerve was examined by real-time PCR.

Results: : Western blot analysis showed transient but significant increase in the level of p-CREB protein in the retina and the optic nerve 1day after TNF-α injection compared with those after PBS injection. Immunohistochemistry of p-CREB confirmed an increase of p-CREB immunoreactivity in the optic nerve 1 day after TNF-α injection. Double-labeling immunohistochemical study showed substantial colocalization of p-CREB and neurofilament. BDNF mRNA expression was significantly increased in the optic nerve 1 day after TNF-α injection. The reduction in the number of axons induced by TNF-α was significantly prevented by the exogenous BDNF .

Conclusions: : Early transient increase in p-CREB may be a manifestation for endogenous protective function as accompanied with up-regulation of BDNF in the optic nerve. Although BDNF has been reported to have beneficial effect on neuronal cell body, our data suggest that BDNF also may rescue axonal death.

Keywords: neuroprotection • optic nerve • growth factors/growth factor receptors 
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