Elucidation of the mechanism of suppression of outer nulear layer cell death of retinitis pigmentosa model rat retina by rapamycin.

• Project/Area Number: 15K10883
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Chubu University
• Principal Investigator: NISHIZAWA Yuji 中部大学, 生命健康科学部, 教授 (80252229)
• Co-Investigator(Kenkyū-buntansha): 竹内 環 中部大学, 全学共通教育部, 助教 (90392018)
• Co-Investigator(Renkei-kenkyūsha): SAKAKIBARA Akira 中部大学, 生命健康科学部, 准教授 (20510217) ; HIRAKO Yoshiaki 名古屋大学, 大学院理学系研究科, 講師 (50377909) ; KONDO Mineo 三重大学, 大学院医学系研究科, 教授 (80303642)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 網膜色素変性症 / 網膜 / 視細胞 / ロドプシン / トランスジェニックラット / ラパマイシン / アポトーシス / オートファジー / 小胞体ストレス / エボジアミン

Outline of Final Research Achievements

We successfully transiently suppressed visual photoreceptor death by microinjecting rapamycin to the eyeball of rhodopsin P347L transgenic rat (Tg rat), a retinal pigmentosa (RP) model rat. By rapamycin injection, mRNA expression levels of Bip and CHOP of the Tg rat retina were transiently and significantly decreased. On the other hand, mRNA expression level of Atg5 consistently increased significantly in Tg rats. Also, the fluorescence intensity of LC3 was greatly enhanced in visual cells after injection of rapamycin. From the above results, it was suggested that autophagy was transiently enhanced by injection of rapamycin into the Tg rat eyeball, and the ER stress response improved and apoptosis was delayed.

Research Products

• [Journal Article] Modulation of the sphingolipid rheostat is involved in paclitaxel resistance of the human prostate cancer cell line PC3-PR (2016)
  • Author(s): Yuka Aoyama, Sayaka Sobue, Naoki Mizutani, Chisato Inoue, Yoshiyuki Kawamoto, Yuji Nishizawa, Masatoshi Ichihara, Mamoru Kyogashima, Motoshi Suzuki, Yoshinoti Nozawa, Takashi Murate
  • Journal Title: Biochem Biophys Res Commun Volume: 486 Issue: 2 Pages: 551-557
  • DOI: 10.1016/j.bbrc.2017.03.084
  • Peer Reviewed / Open Access
• [Journal Article] Malondialdehyde induces autophagy dysfunction and VEGF secretion in the retinal pigment epithelium in age-related macular degeneration. (2016)
  • Author(s): Ye F, Kaneko H, Hayashi Y, Takayama K, Hwang SJ, Nishizawa Y, Kimoto R, Nagasaka Y, Tsunekawa T, Matsuura T, Yasukawa T, Kondo T, Terasaki H.
  • Journal Title: Free Radic Biol Med Volume: 23 Pages: 121-134
  • DOI: 10.1016/j.freeradbiomed.2016.02.027
  • NAID: 120005866829
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A Naturally Occurring Canine Model of Autosomal Recessive Congenital Stationary Night Blindness. (2015)
  • Author(s): Mineo Kondo, Gautami Das, Ryoetsu Imai, Evelyn Santana, Tomio Nakashita, Miho Imawaka, Kosuke Ueda, Hirohiko Ohtsuka, Kazuhiko Sakai, Takehiro Aihara, Kumiko Kato, Masahiko Sugimoto, Shinji Ueno, Yuji Nishizawa, Gustavo D. Aguirre, Keiko Miyadera.
  • Journal Title: PloS One Volume: 10 Issue: 9 Pages: e0137072-e0137072
  • DOI: 10.1371/journal.pone.0137072
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 網膜色素変性症モデルラット網膜におけるラパマイシンの効果の解析 (2017)
  • Author(s): 井上千聖、西沢祐治
  • Organizer: コ・メディカル形態機能学会 第16回学術集会
• [Presentation] 網膜色素変性症モデルラット網膜における小胞体ストレス応答の解析 (2017)
  • Author(s): 西沢祐治、井上千聖
  • Organizer: コ・メディカル形態機能学会 第16回学術集会