Molecular relationship between axonal transported substance and microglia in TNF-α-induced optic neuropathy

• Project/Area Number: 20791285
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Ophthalmology
• Research Institution: St.Marianna University School of Medicine
• Principal Investigator: KITAOKA Yasuhsi St.Marianna University School of Medicine, 医学部, 講師 (10367352)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2008: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: TNF-α / 視神経 / Nmnat1 / 緑内障 / マイクログリア / Neurofilament / Trx1 / エストロゲン / BDNF / 網膜神経節細胞 / オリゴデンドロサイト / CREB

Research Abstract

The levels of Nmnat1 mRNA and protein and of NAD were significantly decreased in the optic nerve but not in the retina in TNF-induced optic neuropathy. Exogenous NAD significantly prevented TNF-induced axonal loss and leaded to the preserved organization of microtubules. The TNF-induced microglial activation was significantly inhibited by NAD treatment. On the other hands, p-CREB and BDNF in oligodendrocytes may serve as a protective moderator for optic nerve axons.

Research Products

• [Journal Article] Axonal and cellbody protection by nicotinamide adenine dinucleotide in tumor necrosis factor-induced optic neuropathy. (2009)
  • Author(s): Kitaoka Y, et al., 他9名
  • Journal Title: J Neuropathol Exp Neurol. 68 Pages: 915-927
  • Peer Reviewed
• [Journal Article] Axonal protection by brain-derived neurotrophic factor associated with CREB phosphorylation in tumor necrosis factor-a-induced optic nerve degeneration. (2009)
  • Author(s): Fujino H, Kitaoka Y, et al., 他6名
  • Journal Title: Acta Neuropathol. 117 Pages: 75-84
  • Peer Reviewed
• [Journal Article] Axonal and cell body protection by nicotinamide adenine dinucleotide intumor necrosis factor-induced optic neuropathy (2009)
  • Author(s): Kitaoka Y, et al.
  • Journal Title: J Neuropathol Exp Neurol 68 Pages: 915-927
  • Peer Reviewed
• [Journal Article] Axonal protection by brain- derived neurotrophic factor associated with CREB phosphorylation in tumor necrosis factor- a- induced optic nerve degeneration (2009)
  • Author(s): Fujino H, et.al.
  • Journal Title: Acta Neuropathol 117 Pages: 75-84
  • Peer Reviewed
• [Journal Article] Effects of unoprostone on phosphorylated extracellular signal-regulated kinase expression in endothelin- 1-induced retinal and optic nerve damage. (2008)
  • Author(s): Munemasa Y, Kitaoka Y, et al., 他6名
  • Journal Title: Vis Neurosci. 25 Pages: 197-208
  • Peer Reviewed
• [Presentation] TNF-α誘発視神経軸索障害及びRGC-5細胞死におけるエストロゲンの保護効果にTrx1が関係する (2009)
  • Author(s): 北岡康史, 他8名
  • Organizer: 第20回日本緑内障学会
  • Place of Presentation: 沖縄
  • Year and Date: 2009-11-14
• [Presentation] 緑内障性視神経症におけるミトコンドリア外膜の透過性制御と神経保護の可能性 (2009)
  • Author(s): 宗正泰成、北岡康史, 他2名
  • Organizer: 第20回日本緑内障学会
  • Place of Presentation: 沖縄
  • Year and Date: 2009-11-14
• [Presentation] NMDA硝子体投与後早期における軸索変性機序の解明 (2009)
  • Author(s): 栗林純子、北岡康史, 他3名
  • Organizer: 第20回日本緑内障学会
  • Place of Presentation: 沖縄
  • Year and Date: 2009-11-14
• [Presentation] TNF-α誘発視神経軸索障害及びRGC-5細胞死におけるエストロゲンの保護効果にTrx1が関与する (2009)
  • Author(s): 北岡康史, (他8名)
  • Organizer: 第20回日本緑内障学会
  • Place of Presentation: 沖縄コンベンションセンター(沖縄県)
  • Year and Date: 2009-11-14
• [Presentation] 緑内障性視神経症におけるミトコンドリア外膜の透過性制御と神経保護の可能性 (2009)
  • Author(s): 宗正泰成, (他3名)
  • Organizer: 第20回日本緑内障学会
  • Place of Presentation: 沖縄コンベンションセンター(沖縄県)
  • Year and Date: 2009-11-14
• [Presentation] NMDA硝子体投与後早期における軸索変性機序の解明 (2009)
  • Author(s): 栗林純子, (他4名)
  • Organizer: 第20回日本緑内障学会
  • Place of Presentation: 沖縄コンベンションセンター(沖縄県)
  • Year and Date: 2009-11-14
• [Presentation] 視神経軸索障害モデルの網膜神経節細胞死の比較検討 (2009)
  • Author(s): 北岡康史, 他3名
  • Organizer: 第29回日本眼薬理学
  • Place of Presentation: 品川
  • Year and Date: 2009-09-12
• [Presentation] 視神経軸索障害モデルの網膜神経節細胞死の比較検討 (2009)
  • Author(s): 北岡康史, (他3名)
  • Organizer: 第29回日本眼薬理学会
  • Place of Presentation: 昭和大学(東京都)
  • Year and Date: 2009-09-12
• [Presentation] Axonal protection in TNF-induced and high IOP-induced 0ptic nerve de generation (2009)
  • Author(s): Kitaoka Y
  • Organizer: Glaucoma Summer Camp
  • Place of Presentation: Lake Biwa
  • Year and Date: 2009-07-31
• [Presentation] Modulation of mitochondrial function in the optic nerve of rat glaucoma model. (2009)
  • Author(s): Munemasa Y, Kitaoka Y, 他2名
  • Organizer: 2009 ARVO annual meeting
  • Place of Presentation: Florida
  • Year and Date: 2009-05-06
• [Presentation] Modulation of mitochondrial function in the optic nerve of rat glaucoma model (2009)
  • Author(s): Munemasa Y, et al.
  • Organizer: 2009 ARV0 annual meeting
  • Place of Presentation: フロリダ
  • Year and Date: 2009-05-06
• [Presentation] Involvement of Trx 1 in protective effect of 17f3-estradiol against TNF-a-induced axonal and cell body degeneration. (2009)
  • Author(s): Kitaoka Y, 他3名
  • Organizer: 2009 ARVO annual meeting
  • Place of Presentation: Florida
  • Year and Date: 2009-05-04
• [Presentation] Involvement of Trxl in protective effect of 17β -estradiol against TNF-α-induced axonal and cell body degeneration (2009)
  • Author(s): Kitaoka Y, et al.
  • Organizer: 2009 ARVO annual meeting
  • Place of Presentation: フロリダ
  • Year and Date: 2009-05-04
• [Presentation] シンポジウム3「緑内障治療の未来」視神経変性の分子機構と軸索保護 (2008)
  • Author(s): 北岡康史
  • Organizer: 第19回日本緑内障学会
  • Place of Presentation: 大阪
  • Year and Date: 2008-09-13
• [Presentation] シンポジウム3「緑内障治療の未来」視神経変性の分子機構と軸索保護 (2008)
  • Author(s): 北岡康史
  • Organizer: 第19回日本緑内障学会
  • Place of Presentation: 大阪府
  • Year and Date: 2008-09-13
• [Presentation] Distribution of ROCK2 in TNF-a-induced optic nerve degeneration. (2008)
  • Author(s): Kitaoka Y, Kitaoka Y, 他4名
  • Organizer: 2008 ARVO annual meeting
  • Place of Presentation: Florida
  • Year and Date: 2008-04-30
• [Presentation] Decreased Nicotinamide Adenine Dinucleotide (NAD) levels and the effect of exogenous NAD on microglia activation in TNF-a-induced optic nerve degeneration. (2008)
  • Author(s): Kitaoka Y, 他9名
  • Organizer: 2008 ARVO annual meeting
  • Place of Presentation: Florida
  • Year and Date: 2008-04-30
• [Presentation] Phosphorylation of CREB and up-regulation of BDNF in TNF-a-induced optic nerve degeneration. (2008)
  • Author(s): Fujino H, Kitaoka Y, 他4名
  • Organizer: 2008 ARVO annual meeting
  • Place of Presentation: Florida
  • Year and Date: 2008-04-30
• [Presentation] Involvement of ERa in protective effect of 17p-estradiol against TNF-a-induced optic nerve degeneration. (2008)
  • Author(s): Hayashi Y, Kitaoka Y, 他3名
  • Organizer: 2008 ARVO annual meeting
  • Place of Presentation: Florida
  • Year and Date: 2008-04-30
• [Presentation] Distribution of ROCK2 in TNF-α-induced optic nerve degeneration (2008)
  • Author(s): Kitaoka Y, et.al.
  • Organizer: 2008 ARVO annual meeting
  • Place of Presentation: フロリダ
  • Year and Date: 2008-04-30
• [Presentation] Decreased Nicotinamide Adenine Dinucleotide (NAD) levels and the effect of exogenous NAD on microglia activation in TNF- a- induced optic nerve degeneration (2008)
  • Author(s): Kitaoka Y, et.al.
  • Organizer: 2008 ARVO annual meeting
  • Place of Presentation: フロリダ
  • Year and Date: 2008-04-30
• [Presentation] Phosphorylation of CREB and up- regulation of BllNF in TINE- a- induced ontic nerve degeneration (2008)
  • Author(s): Fujino H, et.al.
  • Organizer: 2008 ARVO annual meeting
  • Place of Presentation: フロリダ
  • Year and Date: 2008-04-30
• [Presentation] Involvement of ERa in protective effect of 178- estradiol against TNF- a- induced optic nerve degeneration (2008)
  • Author(s): Hayashi Y, et.al.
  • Organizer: 2008 ARVO annual meeting
  • Place of Presentation: フロリダ
  • Year and Date: 2008-04-30
• [Presentation] Early elevation of OX2 antigen and OX2 receptor in TNF-a-induced optic nerve degeneration. (2008)
  • Author(s): Takeda H, Kitaoka Y, 他4名
  • Organizer: 2008 ARVO annual meeting
  • Place of Presentation: Florida
  • Year and Date: 2008-04-29
• [Presentation] Early elevation of OX2 antigen and OX2 receptor in TNF-a-induced optic nerve degeneration (2008)
  • Author(s): Takeda H, et.al.
  • Organizer: 2008 ARVO annual meeting
  • Place of Presentation: フロリダ
  • Year and Date: 2008-04-29