Retinal regeneration due to regulation of natural immunity

• Project/Area Number: 26293373
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Kyushu University (2015-2016); Yamaguchi University (2014)
• Principal Investigator: Sonoda Koh-Hei 九州大学, 医学(系)研究科(研究院), 教授 (10294943)
• Co-Investigator(Kenkyū-buntansha): 木村 和博 山口大学, 医学(系)研究科(研究院), 講師 (60335255) ; 森重 直行 山口大学, 医学(系)研究科(研究院), 講師 (40346565) ; 柳井 亮二 山口大学, 医学部附属病院, 講師 (10346554) ; 藏滿 保宏 山口大学, 医学(系)研究科(研究院), 准教授 (50281811) ; 山崎 晶 九州大学, 生体防御医学研究所, 教授 (40312946) ; 中村 和行 山口大学, その他部局等, 名誉教授 (90107748)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000); Fiscal Year 2016: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2015: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
• Keywords: 自然炎症 / アラーミン / 内在性幹細胞 / 網膜再生 / 自然免疫 / 幹細胞 / 炎症 / プロテオミクス / 自然炎症制御 / 網膜自己再生 / RPE / マクロファージ

Outline of Final Research Achievements

We found that Mincle and NLRs are critical in the process of natural immune response (IL-1a, IL-6 production) in the inflamed retina. During the regional inflammation, internal stem cells which modified muller glia cells were generated and activated. We purified these cells and analyzed specific proteins, and found DRP-2 and DRP-3 proteins (long isoforme) were elevated. Adding these factors into the cultured murine muller cells, they increased the proliferation ability and showed partial increase of nestin. We concluded these factors are critical for " inflammation" indued internal stem cells.

Research Products

• [Journal Article] Changes in metabolic proteins in ex vivo rat retina during glutamate-induced neural progenitor cell induction. (2016)
  • Author(s): Tokuda K, Kuramitsu Y, Baron B, Kitagawa T, Tokuda N, Kobayashi M, Kimura K, Sonoda KH, Nakamura K.
  • Journal Title: Mol Cell Biochem. Volume: 419 Issue: 1-2 Pages: 177-84
  • DOI: 10.1007/s11010-016-2769-z
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Up-regulation of DRP-3 long isoform during the induction of neural progenitor cells by glutamate treatment in the ex vivo rat retina. (2015)
  • Author(s): Tokuda K, Kuramitsu Y, Byron B, Kitagawa T, Tokuda N, Kobayashi D, Nagayama M, Araki N, Sonoda K , Nakamura K.
  • Journal Title: Biochem Biophys Res Commun Volume: 463 Issue: 4 Pages: 593-599
  • DOI: 10.1016/j.bbrc.2015.05.102
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Up-regulation of semaphorin 4A expression in human retinal pigment epithelial cells by PACAP released from cocultured neural cells (2015)
  • Author(s): Ko JA, Hirata J, Yamane K, Sonoda KH, Kiuchi Y.
  • Journal Title: Cell Biochem Funct Volume: 33 Issue: 1 Pages: 29-36
  • DOI: 10.1002/cbf.3082
  • Peer Reviewed
• [Journal Article] Development and validation of new diagnostic criteria for acute retinal necrosis. (2015)
  • Author(s): Takase H, Okada AA, Goto H, Mizuki N, Namba K, Ohguro N, Sonoda KH, Tomita M, Keino H, Kezuka T, Kubono R, Mizuuchi K, Shibuya E, Takahashi H, Yanai R, Mochizuki M
  • Journal Title: Jpn J Ophthalmol Volume: 59(1) Issue: 1 Pages: 14-20
  • DOI: 10.1007/s10384-014-0362-0
  • NAID: 210000165197
  • Peer Reviewed / Open Access
• [Journal Article] A stem cell medium containing neural stimulating factor induces a pancreatic cancer stem-like cell-enriched population. (2014)
  • Author(s): Watanabe Y, Yoshimura K, Yoshikawa K, Tsunedomi R, Shindo Y, Matsukuma S, Maeda N, Kanekiyo S, Suzuki N, Kuramasu A, Sonoda K, Tamada K, Kobayashi S, Saya H, Hazama S and Oka M
  • Journal Title: Int J Oncol Volume: 45 Issue: 5 Pages: 1857-1866
  • DOI: 10.3892/ijo.2014.2603
  • Peer Reviewed / Open Access
• [Journal Article] Evaluation of the long-term efficacy and safety of infliximab treatment for uveitis in Behçet's disease: a multicenter study. (2014)
  • Author(s): Takeuchi M, Kezuka T, Sugita S, Keino H, Namba K, Kaburaki T, Maruyama K, Nakai K, Hijioka K, Shibuya E, Komae K, Hori J, Ohguro N, Sonoda KH, Mizuki N, Okada AA, Ishibashi T, Goto H, Mochizuki M
  • Journal Title: Ophthalmology Volume: 121(10) Issue: 10 Pages: 1877-1884
  • DOI: 10.1016/j.ophtha.2014.04.042
  • Peer Reviewed / Open Access
• [Journal Article] EBI3 is pivotal for the initiation of experimental autoimmune uveitis. (2014)
  • Author(s): Takeda A, Hasegawa E, Fukuhara T, Hirakawa S, Yamada H, Yang Y, Yoshimura T, Hisatomi T, Oshima Y, Yoshida H, Sonoda KH, Ishibashi T
  • Journal Title: Exp Eye Res Volume: 125 Pages: 107-113
  • DOI: 10.1016/j.exer.2014.06.004
  • Peer Reviewed
• [Journal Article] Cytochrome P450-generated metabolites derived from ω-3 fatty acids attenuate neovascularization (2014)
  • Author(s): Yanai R，Mulki L，Hasegawa E，Takeuchi K，Sweigard H，Suzuki J，Gaissert P，Vavvas DG，Sonoda KH，Rothe M，Schunck WH，Miller JW ，Connor KM
  • Journal Title: Proc Natl Acad Sci USA Volume: 111 Issue: 26 Pages: 9603-9608
  • DOI: 10.1073/pnas.1401191111
  • Peer Reviewed
• [Journal Article] Inhibition by All-Trans-Retinoic Acid of Transforming Growth Factor-β-Induced Collagen Gel Contraction Mediated by Human Tenon Fibroblasts (2014)
  • Author(s): Liu Y，Kimura K，Orita T，Teranishi S，Suzuki K，Sonoda KH
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 55 Issue: 7 Pages: 4199-4205
  • DOI: 10.1167/iovs.13-13572
  • Peer Reviewed
• [Presentation] The role of IL-27 in the formation of ocular inflammatory disease (2015)
  • Author(s): Sonoda KH
  • Organizer: 2015 Asia-ARVO
  • Place of Presentation: 神奈川県横浜市（パシフィコ横浜）
  • Year and Date: 2015-02-18
  • Invited
• [Presentation] 高齢者の非感染性ぶどう膜炎は眼局所治療で治す！ (2014)
  • Author(s): 園田 康平
  • Organizer: 第48回日本眼炎症学会
  • Place of Presentation: 東京都千代田区（東京国際フォーラム）
  • Year and Date: 2014-07-05
  • Invited
• [Presentation] 自然免疫系が修飾する後眼部疾患 (2014)
  • Author(s): 園田 康平
  • Organizer: 第48回日本眼炎症学会
  • Place of Presentation: 東京都千代田区（東京国際フォーラム）
  • Year and Date: 2014-07-05
  • Invited
• [Presentation] Primary Care for Patients with Uveitis (Learning from Clinical Uveitic Cases) (2014)
  • Author(s): 園田 康平
  • Organizer: WOC2014
  • Place of Presentation: 東京都千代田区（東京国際フォーラム）
  • Year and Date: 2014-04-04
  • Invited