Upregulation of IGF-I in the goldfish retinal ganglion cells during the early stage of optic nerve regeneration

• Koriyama, Yoshiki

• Homma, Keiko

• Sugitani, Kayo

• Higuchi, Yoshihiro

• Matsukawa, Toru

• Murayama, Daisuke

• Kato, Satoru

抄録

金沢大学医薬保健研究域　医学系

Goldfish retinal ganglion cells (RGCs) can regrow their axons after optic nerve injury. However, the reason why goldfish RGCs can regenerate after nerve injury is largely unknown at the molecular level. To investigate regenerative properties of goldfish RGCs, we divided the RGC regeneration process into two components: (1) RGC survival, and (2) axonal elongation processes. To characterize the RGC survival signaling pathway after optic nerve injury, we investigated cell survival/death signals such as Bcl-2 family members in the goldfish retina. Amounts of phospho-Akt (p-Akt) and phospho-Bad (p-Bad) in the goldfish retina rapidly increased four- to five-fold at the protein level by 3-5 days after nerve injury. Subsequently, Bcl-2 levels increased 1.7-fold, accompanied by a slight reduction in caspase-3 activity 10-20 days after injury. Furthermore, level of insulin-like growth factor-I (IGF-I), which activates the phosphatidyl inositol-3-kinase (PI3K)/Akt system, increased 2-3 days earlier than that of p-Akt in the goldfish retina. The cellular localization of these molecular changes was limited to RGCs. IGF-I treatment significantly induced phosphorylation of Akt, and strikingly induced neurite outgrowth in the goldfish retina in vitro. On the contrary, addition of the PI3K inhibitor wortmannin, and IGF-I antibody inhibited Akt phosphorylation and neurite outgrowth in an explant culture. Thus, we demonstrated, for the first time, the signal cascade for early upregulation of IGF-I, leading to RGC survival and axonal regeneration in adult goldfish retinas through PI3K/Akt system after optic nerve injury. The present data strongly indicate that IGF-I is one of the most important molecules for controlling regeneration of RGCs after optic nerve injury. © 2007 Elsevier Ltd. All rights reserved.

収録刊行物

• Neurochemistry International

  Neurochemistry International 50 (5), 749-756, 2007-04-01

  Elsevier BV

キーワード

• Goldfish
• IGF-I
• Optic nerve regeneration
• p-Akt
• Retina
• Retinal ganglion cells
• Survival

詳細情報

• CRID: 1050001335948206464
• NII論文ID: 120001450995
• NII書誌ID: AA0032399X
• ISSN: 01970186
• Web Site: http://hdl.handle.net/2297/18637
• 本文言語コード: en
• 資料種別: journal article
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