Analysis of molecular basis of retinal glial cells and their roles in retinal degeneration diseases

• Project/Area Number: 15K15628
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Ophthalmology
• Research Institution: The University of Tokyo
• Principal Investigator: Watanabe Sumiko 東京大学, 医科学研究所, 特任教授 (60240735)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 網膜 / ミュラーグリア / マイクログリア / 変性 / 遺伝子発現 / ヒストンメチル化 / ミューラーグリア / 視細胞変性

Outline of Final Research Achievements

We established technic to purify photoreceptor, Mueller glia, and microglia by using multiple cell surface antigens and a cell sorter. Then, these retinal subsets were purified from normal and photoreceptor-degenerated retina, and RNA-seq was performed using the fractions. Genes specifically up-regulated in each retinal subtype were identified by bio-informatics technics. Time course of gene expression was examined, and interaction of the subtypes through cytokines and chemokines during retinal degeneration was examined from the results.

Research Products

• [Journal Article] Conditional rod photoreceptor ablation reveals Sall1 as a microglial marker and regulator of microglial morphology in the retina. (2016)
  • Author(s): Koso H, Tsuhako A, Lai CY, Baba Y, Otsu M, Ueno K, Nagasaki M, Suzuki Y, Watanabe S.
  • Journal Title: Glia Volume: 64 Issue: 11 Pages: 2005-2024
  • DOI: 10.1002/glia.23038
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Regulation of retinal development via the epigenetic modification of histone H3. (2016)
  • Author(s): Watanabe, S., Murakami A
  • Journal Title: Adv Exp Med Biol Volume: 854 Pages: 635-641
  • DOI: 10.1007/978-3-319-17121-0_84
  • ISBN: 9783319171203, 9783319171210
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Expression pattern of Ccr2 and Cx3cr1 in inherited retinal degeneration. (2015)
  • Author(s): Kohno H, Koso H, Okano K, Sundermeier TR, Saito S, Watanabe S, Tsuneoka H, Sakai T.
  • Journal Title: Journal of Neuroinflammation Volume: 12 Issue: 1 Pages: 188-188
  • DOI: 10.1186/s12974-015-0408-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] MicroRNA-7a regulates Muller glia differentiation by attenuating Notch3 expression (2015)
  • Author(s): Baba, Y., Aihara, Y., Watanabe, S
  • Journal Title: Exp Eye Res Volume: 138 Pages: 59-65
  • DOI: 10.1016/j.exer.2015.06.022
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Roles Histone H3K27 tri-methylase Ezh2 in retinal proliferation and differentiation (2015)
  • Author(s): ida, A., Iwagawa, T., Baba, Y.,Satoh, S., Mochizuki, Y., Nakauchi, H., Furukawa, T., Koseki, H., Murakami, A., Watanabe, S.
  • Journal Title: Developmental Neurobiology Volume: - Issue: 9 Pages: 3751-3756
  • DOI: 10.1002/dneu.22261
  • Peer Reviewed
• [Presentation] 視細胞変性の病態メカニズムの分子基盤の解明を目指して (2016)
  • Author(s): 渡辺すみ子
  • Organizer: 順天堂アレルギー研究会
  • Place of Presentation: 大洗シーサイドホテル（茨城県、大洗町）
  • Year and Date: 2016-03-09
  • Invited
• [Presentation] 視細胞変性におけるマイクログリアの役割とその治療標的としての可能性 (2015)
  • Author(s): 渡辺すみ子
  • Organizer: 長崎大学医歯薬セミナー
  • Place of Presentation: 長崎大学医学部（長崎県、長崎市）
  • Year and Date: 2015-10-02
  • Invited