Analysis of the molecular mechanism for human pigment epithelium-derived factor (hPEDF) mediated photoreceptor cell neuroprotection

• Project/Area Number: 20791259
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Ophthalmology
• Research Institution: Kyushu University
• Principal Investigator: IKEDA Yasuhiro Kyushu University, 大学病院, 助教 (20380389)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2008: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 眼科学 / 網膜色素変性 / 神経保護 / 遺伝子治療 / 視細胞保護 / ヒト色素上皮由来因子 / サル由来レンチウイルスベクター / アポトーシス誘導因子 / 網膜色素変 / ヒト色素上皮由来因子(hPEDF) / サル由来レンチウイルス(SIV)ベクター / アポトーシス誘導因子(AIF)

Research Abstract

The key observations made in this study are as follows: 1) PEDF efficiently rescued apoptosis induced by serum starvation in R28 cells derived from rat retina ; 2) AIF but not caspases was a key effector of the serum starvation-induced apoptosis, and PEDF prevented AIF from translocating into the nucleus after serum starvation; 3) Nuclear translocation of AIF was also observed in apoptotic photoreceptors of RCS rats, and was significantly inhibited by retinal gene transfer of PEDF in vivo, resulting in a substantial delay in retinal degeneration; and 4) PEDF prevented the AIF release through upregulation of Bcl-2.

Research Products

• [Journal Article] Inhibition of choroidal neovascularization via brief subretinal exposure to a newly developed lentiviral vector pseudotyped with Sendai virus envelope proteins. (2010)
  • Author(s): Murakami Y, Ikeda Y, Yonemitsu Y, Miyazaki M, Inoue M, Hasegawa M, Sueishi K, Ishibashi T
  • Journal Title: Hum Gene Ther. 21 Pages: 199-209
• [Journal Article] Inhibition of nuclear translocation of apoptosis-inducing factor is an essential mechanism of the neuroprotective activity of pigment epithelium-derived factor in a rat model of retinal degeneration (2008)
  • Author(s): Murakami Y, Ikeda Y, et.al
  • Journal Title: Am J Pathol 173 Pages: 1326-1338
  • Peer Reviewed
• [Presentation] Regulation of mitochondrial release of apoptosis-inducing factor is a mechanism for neuroprotective activity of pigment epithelium-derived factor in retinal degeneration (2008)
  • Author(s): Murakami Y, Ikeda Y, et.al
  • Organizer: The Association for Research in Vision and Ophthalmoloay (ARVO)
  • Place of Presentation: アメリカ、フロリダ州、フォートローダーデール
  • Year and Date: 2008-04-28