Characterization of mouse models for age-related macular degeneration

• Project/Area Number: 24592664
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: 独立行政法人国立病院機構(東京医療センター臨床研究センター)
• Principal Investigator: NAKAYAMA MAO 独立行政法人国立病院機構(東京医療センター臨床研究センター), 分子細胞生物学研究部, 研究員 (20624810)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 加齢黄斑変性 / 感受性遺伝子 / HTRA1 / ARMS2 / トランスジェニックマウス / 喫煙 / 眼分子生物学 / 眼生化学

Outline of Final Research Achievements

Genetic and environmental factors are believed to be involved in the onset of age-related macular degeneration (AMD).We generated three mouse lines that overexpressed mouse HtrA1, human ARMS2 and ARMS2(A69S) throughout the entire mouse body. CNV similar to human AMD was observed progression in HtrA1 Tg mouse at 12-month-old. Exposure to mainstream cigarette smoke enhanced the CNV rate in HtrA1 Tg mouse. Our data suggested that HtrA1 overexpression alone is a strong risk factor for wet AMD, which is the predominant form of AMD in the Japanese population.

Research Products

• [Journal Article] Overexpression of HtrA1 and exposure to mainstream cigarette smoke leads to choroidal neovascularization and subretinal deposits in aged mice (2014)
  • Author(s): Mao Nakayama, Daisuke Iejima, Masakazu Akahori, Junzo Kamei, Asako Goto, Takeshi Iwata
  • Journal Title: IOVS (investigative ophthalmology＆visual science) Volume: 55 Issue: 10 Pages: 6514-6523
  • DOI: 10.1167/iovs.14-14453
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Human HTRA1 expression is enhanced by indel mutation in the HTRA1 regulatory element region (2015)
  • Author(s): Daisuke Iejima, Mao Nakayama, Toru Noda, Atsushi Mizota, Takeshi Iwata
  • Organizer: 2015 ARVO
  • Place of Presentation: Denver, Colorado, USA
  • Year and Date: 2015-05-03 – 2015-05-07
• [Presentation] 滲出型加齢黄斑変性の感受性遺伝子領域ARMS2/HTRA1の転写機能解析 (2015)
  • Author(s): 家島 大輔、中山 真央、川村 雄一、野田 徹、岩田 岳
  • Organizer: 第１９回眼科分子生物学研究会
  • Place of Presentation: 岐阜県岐阜市湊町１０番地十八楼
  • Year and Date: 2015-02-28 – 2015-03-01
• [Presentation] Characterization of HTRA1 Promoter in Patients with Exudative Age-Related Macular Degeneration (2015)
  • Author(s): Daisuke Iejima, Mao Nakayama, Takeshi Itabashi, Yuich Kawamura, Masakazu Akahori, Toru Noda, Takeshi Iwata
  • Organizer: 2015 Asia ARVO
  • Place of Presentation: Yokohama, Japan
  • Year and Date: 2015-02-16 – 2015-02-19
• [Presentation] Characterization of HTRA1 promoter in patients with exudative age-related macular degeneration and induction of choroidal neovascularization by overexpression of HtrA1 in aged mice (2014)
  • Author(s): Mao Nakayama, Daisuke Iejima, Takeshi Itabashi, Yuichi Kawamura, Masakazu Akahori , Toru Noda, Takeshi Iwata
  • Organizer: ISER2014 (XXIth International Society for Eye Research Biennial Meeting)
  • Place of Presentation: San Francisco, California, USA
  • Year and Date: 2014-07-20 – 2014-07-24
• [Presentation] Characterization of HTRA1 promoter in patients with exudative age-related macular degeneration and induction of choroidal neovascularization by overexpression of HtrA1 in aged mice (2014)
  • Author(s): Mao Nakayama, Daisuke Iejima, Takeshi Itabashi, Yuichi Kawamura, Masakazu Akahori , Toru Noda, Takeshi Iwata
  • Organizer: RD2014 (XVIth International Symposium on Retinal Degeneration)
  • Place of Presentation: Pacific Grove, California, USA
  • Year and Date: 2014-07-13 – 2014-07-18
• [Presentation] 加齢黄斑変性感受性遺伝子HtrA1のトランスジェニックマウスの病態と習慣因子（喫煙）の影響 (2013)
  • Author(s): 中山真央、家島大輔、赤堀正和、亀井淳三、岩田岳
  • Organizer: RRM (Retinal Research Meeting)
  • Place of Presentation: 東京
• [Presentation] Overexpression of HtrA1 and Smoking Evokes Choroidal Neovascularization and Retinal Deposit in Aged Mice (2013)
  • Author(s): 中山 真央
  • Organizer: ＡＲＶＯ（The Association for Research in Vision and Ophthalmology)
  • Place of Presentation: アメリカ・シアトル
• [Remarks] 独立行政法人国立病院機構東京医療センター臨床研究センター感覚器センター分子細胞生物学研究部
  • URL: http://www.kankakuki.go.jp/lab_e.html