Possible application of siRNA and antisense therapies for optic nerve degeneration

• Project/Area Number: 19592045
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: St.Marianna University School of Medicine
• Principal Investigator: UENO Satoki St.Marianna University School of Medicine, 医学部, 教授 (20109010)
• Co-Investigator(Kenkyū-buntansha): KITAOKA Yasushi 聖マリアンナ医科大学, 医学部, 講師 (10367352)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2007: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 眼科学 / siRNA / オリゴヌクレオチド / 視神経 / 緑内障 / TNF-α / オリゴデンドロサイト / NMDA / エンドセリン / アンチセンスオリゴヌクレオチド / 網膜神経節細胞

Research Abstract

エンドセリン誘発網膜視神経障害でリン酸化ERKは網膜で一過性に上昇し、視神経では遅れて上昇することが確認され、この上昇は保護的に働いていることが確認された。またsiRNAの浸透度に関して、硝子体注射で網膜神経節細胞の中に入ることを確認した。CRE decoyオリゴヌクレオチドにより、TNF-αによる内因性のBDNF上昇は有意に抑制され、その上昇は内因性の保護機構であることが示唆された。siRNAおよびオリゴヌクレオチドが視神経変性疾患モデルにある程度有用であることが示唆された。

Research Products

• [Journal Article] Axonal protection by brain-derived neurotrophic factor associated with CREB phosphorylation in tumor necrosis factor-α-induced optic nerve degeneration (2009)
  • Author(s): Fujino H, Kitaoka Y, (他5名), Ueno S
  • Journal Title: Acta Neuropathol 117 Pages: 75-84
  • Peer Reviewed
• [Journal Article] Axonal protection by brain-derived neurotrophic factor associa ted with CREB phosphorylation in tumor necrosis factor-α-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, Hayashi Y, (他4名) Ueno S
  • Journal Title: Vis Neurosci Pages: 197-208
  • 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, et. al.
  • Journal Title: Vis. Neurosci. (In press)
  • Peer Reviewed
• [Journal Article] Calcium/calmodulin-dependent protein kinase II regulates the phosphorylation of CREB in NMDA-induced retinal neurotoxicity (2007)
  • Author(s): Takeda H, Kitaoka Y, (他6名), Ueno S
  • Journal Title: Brain Res 1184 Pages: 306-315
  • Peer Reviewed
• [Journal Article] Calcium/calmodulin-dependent protein kinase II regulates the phosphory lation of CREB in NMDA-induced retinal neurotoxicity. (2007)
  • Author(s): Takeda H, et. al.
  • Journal Title: Brain Res. 1184 Pages: 306-315
  • Peer Reviewed
• [Presentation] TNF-α誘発視神経障害におけるBDNFのCREBリン酸化を介する軸索保護 (2008)
  • Author(s): 北岡康史、上野聰樹(他6名)
  • Organizer: 第28回日本眼薬理学会
  • Place of Presentation: 岡山
  • Year and Date: 2008-09-20
• [Presentation] 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回日本緑内障学会シンポジウム3
  • 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-α-induced optic nerve degeneration (2008)
  • Author(s): Kitaoka Y, Kitaoka Y, (他3名), Ueno S
  • 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-α-induced optic nerve degeneration (2008)
  • Author(s): Kitaoka Y, Hayashi Y,(他7名), Ueno S
  • 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-α-induced optic nerve degeneration (2008)
  • Author(s): Fujino H, Kitaoka Y, (他3名), Ueno S
  • Organizer: 2008 ARVO annual meeting
  • Place of Presentation: Florida
  • Year and Date: 2008-04-30
• [Presentation] Involvement of ERα in protective effect of 17β-estradiol against TNF-α-induced optic nerve degeneration (2008)
  • Author(s): Hayashi Y, Kitaoka Y, (他2名), Ueno S
  • 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 activat ion 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] Phosphorylation of CREB and up-regulation of BDNF in TNF-α-in duced optic 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 ERα in protective effect of17β-estradiol against TNF-α-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-α-induced optic nerve degeneration (2008)
  • Author(s): Takeda H, Kitaoka Y, (他3名), Ueno S
  • 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-α-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
• [Presentation] エンドセリンによる網膜及び視神経障害におけるウノプロストンのp-ERKを介する神経保護効果 (2008)
  • Author(s): 北岡康史、(他4名)、上野聰樹
  • Organizer: 第24回神奈川県緑内障談話会
  • Place of Presentation: 横浜
  • Year and Date: 2008-03-08
• [Presentation] 視神経保護 (2007)
  • Author(s): 北岡康史
  • Organizer: 第27回日本眼薬理学会シンポジウム2
  • Place of Presentation: 岐阜
  • Year and Date: 2007-09-17
• [Presentation] Changes of neurotrophin receptor expression in TNF-α-induced optic nerve degeneration (2007)
  • Author(s): Fujino H, Kitaoka Y, (他4名), Ueno S
  • Organizer: 2007 ARVO annual meeting
  • Place of Presentation: Florida
  • Year and Date: 2007-05-08
• [Presentation] Changes of neurotrophin receptor expression in TNF-α-induced optic nerve degeneration. (2007)
  • Author(s): Fujino H, et. al.
  • Organizer: 2007 ARVO annual meeting
  • Place of Presentation: フロリダ
  • Year and Date: 2007-05-08
• [Presentation] Early phosphorylation of calcium/calmodulin-dependent protein kinase II in NMDA-induced retinal damage (2007)
  • Author(s): Takeda H, Kitaoka Y, (他6名), Ueno S
  • Organizer: 2007 ARVO annual meeting
  • Place of Presentation: Florida
  • Year and Date: 2007-05-06
• [Presentation] europrotective effect of 17β-estradilol against TNF-α-induced axonal degeneration and p-ERK expression (2007)
  • Author(s): Hayashi Y, Kitaoka Y, (他8名), Ueno S
  • Organizer: 2007 ARVO annual meeting
  • Place of Presentation: Florida
  • Year and Date: 2007-05-06
• [Presentation] Early phosphorylation of calcium/calmodulin-dependent protein kinase II in NMDA-induced retinal damage. (2007)
  • Author(s): Takeda H, et. al.
  • Organizer: 2007 ARVO annual meeting
  • Place of Presentation: フロリダ
  • Year and Date: 2007-05-06
• [Presentation] Neuroprotective effect of 17β-estradilol against TNF-α-induced axonal degeneration and p-ERK expression. (2007)
  • Author(s): Hayashi Y, et. al.
  • Organizer: 2007 ARVO annual meeting
  • Place of Presentation: フロリダ
  • Year and Date: 2007-05-06