Investigation for fibrovascular sacr formation of age-related macular degeneration

• Project/Area Number: 17K11454
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Kyushu University
• Principal Investigator: Oshima Yuji 九州大学, 大学病院, 特別教員 (00536237)
• Co-Investigator(Kenkyū-buntansha): 園田 康平 九州大学, 医学研究院, 教授 (10294943)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 加齢黄斑変性 / 脈絡膜新生血管 / 線維性瘢痕 / 網膜萎縮 / 滲出型加齢黄斑変性 / 線維化 / 線維瘢痕化 / 視力維持 / 臨床 / 眼科学

Outline of Final Research Achievements

Participation of regulatory T cell for progression of choroidal neovascularization were investigated using mouse CNV model. IL-10 regressed CNV significantly produced from regulatory T cell by suppressed IL-17 production. This inhibition pathway is an independent of VEGF.
Two hundred ninety-five AMD patients treated with anti-VEGF agent for five years were investigated retrospectively. Best corrected visual acuity was significantly deteriorated for five years. Macular atrophy, fibrovascular proliferation after 5-year treatment was suggested to be associated with basement visual acuity and FA classification, indicating that exudation into neural retina was associated with scarring in long term.

Academic Significance and Societal Importance of the Research Achievements

滲出型加齢黄斑変性は抗VEGF療法により治療可能の疾患となったが、長期的なマネジメントとして瘢痕萎縮病巣をできるだけ小さくする必要がある。今回、VEGFと独立した血管新生に関連する因子としてIL-17が考えられ、今後の治療に結びつく可能性が示唆された。また臨床的には、神経網膜内への滲出が長期の瘢痕萎縮に関連していることが明らかとなり、早期治療の有効性が示された。

Research Products

• [Journal Article] Fundus autofluorescence and retinal sensitivity in fellow eyes of age-related macular degeneration in Japan. (2019)
  • Author(s): Yasukawa T, Mori R, Sawa M, Shinojima A, Hara C, Sekiryu T, Oshima Y, Saito M, Sugano Y, Kato A, Ashikari M, Hirano Y, Asato H, Nakamura M, Matsuno K, Kuno N, Kimura E, Nishiyama T, Yuzawa M, Ishibashi T, Ogura Y, Iida T, Gomi F.
  • Journal Title: PLoS One Volume: 14
  • Peer Reviewed
• [Journal Article] Five-year treatment outcomes following intravitreal ranibizumab injections for neovascular age-related macular degeneration in Japanese patients (2019)
  • Author(s): Wada Iori、Oshima Yuji、Shiose Satomi、Kano Kumiko、Nakao Shintaro、Kaizu Yoshihiro、Yoshida Shigeo、Ishibashi Tatsuro、Sonoda Koh-hei
  • Journal Title: Graefe's Archive for Clinical and Experimental Ophthalmology Volume: 257 Issue: 7 Pages: 1411-1418
  • DOI: 10.1007/s00417-019-04361-8
  • Peer Reviewed
• [Journal Article] Prevalence and Risk Factors for Polypoidal Choroidal Vasculopathy in a General Japanese Population: The Hisayama Study. (2018)
  • Author(s): Fujiwara K, Yasuda M, Hata J, Oshima Y, Hashimoto S, Yoshitomi T, Kiyohara Y, Ishibashi T, Ninomiya T, Sonoda KH.
  • Journal Title: Semin Ophthalmol. Volume: 33 Issue: 6 Pages: 813-819
  • DOI: 10.1080/08820538.2018.1506483
  • Peer Reviewed
• [Journal Article] Genome-wide association study suggests four variants influencing outcomes with ranibizumab therapy in exudative age-related macular degeneration. (2018)
  • Author(s): Akiyama M, Takahashi A, Momozawa Y, Arakawa S, Miya F, Tsunoda T, Ashikawa K, Oshima Y, Yasuda M, Yoshida S, Enaida H, Tan X, Yanagi Y, Yasukawa T, Ogura Y, Nagai Y, Takahashi K, Fujisawa K, Inoue M, Arakawa A, Tanaka K, Yuzawa M, Kadonosono K, Sonoda KH, Ishibashi T, Kubo M.
  • Journal Title: J Hum Genet Volume: 63 Issue: 10 Pages: 1083-1091
  • DOI: 10.1038/s10038-018-0493-0
  • Peer Reviewed
• [Presentation] Patient Preferences for Anti-VEGF Treatment Regimens for Wet Age-Related Macular Degeneration in Japan (2019)
  • Author(s): Yuji Oshima, Takeshi Joko, Yoshimi Nagai, Ryusaburo Mori, Koji Tanaka, Yusuke Hikichi, Tetsushi Komori, Joao Carrasco, Martine Maculaitis, Oliver Will, Kathleen Beusterien, Kanji Takahashi
  • Organizer: ARVO
  • Int'l Joint Research
• [Presentation] 加齢黄斑変性に対するアフリベルセプトtreat and extend法の5年成績 (2019)
  • Author(s): 大島裕司、塩瀬聡美、狩野久美子、石川桂二郎、中尾新太郎、和田伊織、海津嘉弘、長谷川英一、園田康平
  • Organizer: 第36回日本眼循環学会総会
• [Presentation] Five-year outcomes following teat-and-extend therapy using aflibercept for neovascular age-related macular degeneration in Japanese patients (2019)
  • Author(s): Yuji Oshima, Satomi Shiose, Kumiko Kano, Iori Wada, Keijiro Ishikawa, Shintaro Nakao, Yoshihiro Kaitsu, Eiichi Hasegawa, Tatsuro Ishibashi, Koh-hei Sonoda
  • Organizer: The 12th Joint meeting of Chinese-Japanese-Korean Ophthalmologists
  • Int'l Joint Research
• [Presentation] Three-year Outcomes Following Treat-and-Extend Therapy Using Aflibercept for Neovascular Age-related Macular Degeneration in Japanese Patients (2018)
  • Author(s): Hashiguchi N, Oshima Yuji, Shiose S, Kano K, Ishikawa K, Wada I, Funatsu H, Ishibashi T, Sonoda KH
  • Organizer: The 11th Joint Meeting of Japan-China-Korea Ophthalmologists
  • Int'l Joint Research
• [Presentation] The evaluation of disease activity in exudative age-related macular degeneration using en face hyperreflective foci (2018)
  • Author(s): Wada I, Nakao S, Shiose S, Kaizu Y, Yamaguchi M, Arima M, Ishikawa K, Kano K, Oshima Yuji, Ishibashi T, Sonoda KH
  • Organizer: The 11th Joint Meeting of Japan-China-Korea Ophthalmologists
  • Int'l Joint Research
• [Presentation] 滲出型加齢黄斑変性治療における視力およびQOL改善効果の関連性の検討：QUATRO study (2018)
  • Author(s): 大島裕司, 梅野有美、梅田尚靖、永田竜朗、山川良治、内尾英一、近藤寛之、園田康平、石橋達朗
  • Organizer: 第122回日本眼科学会総会
• [Presentation] 加齢黄斑変性に対するアフリベルセプトtreat and extend法の3年成績 (2017)
  • Author(s): 舩津治彦、大島裕司、塩瀬聡美、狩野久美子、中尾新太郎、山口宗男、海津嘉弘、和田伊織、 長谷川英一、徳永瑛子、吉田茂生、 石橋達朗、園田康平
  • Organizer: 第56回日本網膜硝子体学会