Elucidation of the role of inflammation and apoptosis and development of a new target in age-related macular degeneration

• Project/Area Number: 15K10875
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Nagoya City University
• Principal Investigator: Hirano Yoshio 名古屋市立大学, 大学院医学研究科, 講師 (40405163)
• Co-Investigator(Kenkyū-buntansha): 野崎 実穂 名古屋市立大学, 大学院医学研究科, 講師 (00295601) ; 安川 力 名古屋市立大学, 大学院医学研究科, 准教授 (00324632) ; 小椋 祐一郎 名古屋市立大学, 大学院医学研究科, 教授 (70191963)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 脈絡膜新生血管 / 炎症 / アポトーシス / 網膜色素上皮 / 加齢黄斑変性

Outline of Final Research Achievements

Age-related macular degeneration (AMD) is a vision-threatening disease and the number of patients continues to grow. Recently developed anti-vascular endothelial growth factor (VEGF) therapy for choroidal neovascularization (CNV) has revolutionized the treatment in visual improvement. However, there are still ineffective cases or most of the patients need multiple injections of anti-VEGF agents. We aimed to elucidate the pathophysiology of CNV using mouse laser CNV model to investigate a new target for CNV. Inflammation and apoptosis were associated with the CNV formation. Therefore, to control inflammation and apoptosis chould be an alternative therapy to suppress vision loss associated with CNV in AMD.

Research Products

• [Int'l Joint Research] University of Kentucky(United States of America)
• [Int'l Joint Research] University of Kentucky(United States of America)
• [Int'l Joint Research] University of Bern(Switzerland)
• [Journal Article] Clinical characteristics and outcomes of fall-related open globe injuries in Japan. (2018)
  • Author(s): Morikawa Shohei、Japan-Clinical Research of Study (J-CREST) group、Okamoto Yoshifumi、Okamoto Fumiki、Inomoto Naoki、Ishikawa Hiroto、Harimoto Kozo、Ueda Tetsuo、Sakamoto Taiji、Oshika Tetsuro
  • Journal Title: Graefes Arch Clin Exp Ophthalmol. Volume: 印刷中 Pages: 1347-1352
  • DOI: 10.1007/s00417-018-3959-z
  • Peer Reviewed / Open Access
• [Journal Article] Clinical characteristics and visual outcomes of sport-related open globe injuries. (2018)
  • Author(s): Morikawa Shohei、Okamoto Fumiki、Okamoto Yoshifumi、Inomoto Naoki、Ishikawa Hiroto、Ueda Tetsuo、Sakamoto Taiji、Hirano Yoshio、Sawada Osamu、Mori Junya、Takamura Yoshihiro、Oshika Tetsuro
  • Journal Title: Acta Ophthalmol. Volume: 印刷中
  • DOI: 10.1111/aos.13704
  • Peer Reviewed / Open Access
• [Journal Article] cGAS drives noncanonical-inflammasome activation in age-related macular degeneration (2018)
  • Author(s): Terasaki H(他37名）
  • Journal Title: Nat Med Volume: 24 Pages: 50-61
  • DOI: 10.1038/nm.4450
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Wide-field fluorescein and indocyanine green angiography findings in the eyes with Vogt-Koyanagi-Harada disease (2017)
  • Author(s): Kurobe Ryo、Hirano Yoshio、Niwa Naomi、Sugitani Kazuhiko、Yasukawa Tsutomu、Yoshida Munenori、Ogura Yuichiro
  • Journal Title: J OPhthalmic Inflamm Infect Volume: 7
  • DOI: 10.1186/s12348-017-0134-3
  • Peer Reviewed / Open Access
• [Journal Article] Preoperative optical coherence tomography visualization of epiretinal membranes enhances surgical strategies. (2016)
  • Author(s): Suzuki N, Hirano Y, Ichida M, Tomiyasu T, Esaki Y, Yasukawa T, Ogura Y
  • Journal Title: Clin Ophthalmol Volume: 10 Pages: 2297-2302
  • DOI: 10.2147/opth.s122520
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Retinal Hemodynamics Seen on Optical Coherence Tomography Angiography Before and After Treatment of Retinal Vein Occlusion. (2016)
  • Author(s): Suzuki N, Hirano Y, Tomiyasu T, Esaki Y, Uemura A, Yasukawa T, Yoshida M, Ogura Y
  • Journal Title: Invest Ophthalmol Vis Sci. Volume: 57 Pages: 5681-5687
  • DOI: 10.1167/iovs-16-20648
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Microaneurysms cause refractory macular edema in branch retinal vein occlusion. (2016)
  • Author(s): Tomiyasu T, Hirano Y, Yoshida M, Suzuki N, Nishiyama T, Uemura A, Yasukawa T, Ogura Y
  • Journal Title: Sci Rep Volume: 6 Pages: 29445-29445
  • DOI: 10.1038/srep29445
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Intravenous immune globulin suppresses angiogenesis in mice and humans. (2016)
  • Author(s): Yasuma R, Cicatiello V, Mizutani T, Tudisco L, Kim Y, Tarallo V, Bogdanovich S, Hirano Y, erur N, Li S, Yasuma T, Fowler BJ, Wringht CB, Apicella I, Greco A, Brunetti A, Ambati BK, Helmers SB, Lundberg IE, Viklicky O, Leusen JH, Verbeek JS, Gelfand BD, Bastos-Carvalho A, De Falco S, Ambati J
  • Journal Title: Signal Transduct Target Ther Volume: 1 Pages: 15002-15002
  • DOI: 10.1038/sigtrans.2015.2
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Combination therapy with intravitreal tissue plasminogen activator and ranibizumab for subfoveal type 2 choroidal neovascularization. (2016)
  • Author(s): 68. Kachi I, Yasukawa T, Kato A, Takase N, Morita H, Kubota A, Hirano Y, Uemura A, Ogura Y.
  • Journal Title: Jpn J Ophthalmol. Volume: 60 Pages: 179-186
  • DOI: 10.1007/s10384-016-0434-4
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Human IgG1 antibodies suppress angiogenesis in a target-independent manner. (2016)
  • Author(s): Bogdanovich S, Kim Y, Mizutani T, Yasuma R, Tudisco L, Cicatiello V, Bastos-Carvalho A, Kerur N, Hirano Y, Baffi JZ, Tarallo V, Li S, Yasuma T, Arpitha P, Fowler BJ, Wright CB, Apicella I, Greco A, Brunetti A, Ruvo M, Sandomenico A, Nozaki M, Ijima R, Kaneko H, Ogura Y, Terasaki H, Ambati BK, Leusen JHW, et al.
  • Journal Title: Signal Transduct Target Ther Volume: 1 Pages: 15001-15001
  • DOI: 10.1038/sigtrans.2015.1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Microvascular Abnormalities on Optical Coherence Tomography Angiography in Macular Edema Associated with Branch Retinal Vein Occlusion. (2016)
  • Author(s): Suzuki N, Hirano Y, Yoshida M, Tomiyasu T, Uemura A, Yasukawa T, Ogura Y.
  • Journal Title: Am J Ophthalmol Volume: 161 Pages: 126-132
  • DOI: 10.1016/j.ajo.2015.09.038
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Intravitreous immune globulin suppresses angiogenesis in mice and humans. (2016)
  • Author(s): Yasuma R, Cicatiello V, Mizutani T, Tudisco L, Kim Y, Tarallo V, Bogdanovich S, Hirano Y, Kerur N, Li S, Yasuma T, Fowler BJ, Wright CB, Apicella I, Greco A, Brunetti A, Ambati BK, Helmers SB, Lundberg IE, Viklicky O, Leusen JH, Verbeek JS, Gelfand BD, Bastos-Carvalho A, De Falco S, Ambati J.
  • Journal Title: Signal Transduct Target Ther Volume: 1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Human IgG1 antibodies suppress angiogenesis in a target-independent manner. (2016)
  • Author(s): Bogdanovich S, Kim Y, Mizutani T, Yasuma R, Tudisco L, Cicatiello V, Bastos-Carvalho A, Kerur N, Hirano Y, Baffi JZ, Tarallo V, Li S, Yasuma T, Arpitha P, Fowler BJ, Wright CB, Apicella I, Greco A, Brunetti A, Ruvo M, Sandomenico A, Nozaki M, Ijima R, Kaneko H, Ogura Y, Terasaki H, Ambati BK, Leusen JH, et al.
  • Journal Title: Signal Transduct Target Ther Volume: 1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Prevention of increased abnormal fundus autofluorescence with blue light-filtering intraocular lenses. (2015)
  • Author(s): Nagai H, Hirano Y, Yasukawa T, Morita H, Nozaki M, Wolf-Schnurrbusch U, Wolf S, Ogura Y.
  • Journal Title: J Cataract Refract Surg Volume: 41 Pages: 1855-1859
  • DOI: 10.1016/j.jcrs.2015.01.017
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Indocyanine green angiography-guided focal laser photocoagulation for diabetic macular edema (2015)
  • Author(s): Ogura S, Yasukawa T, Kato A, Kuwayama S, Hamada S, Hirano Y, Uemura A, Yoshida M, Ogura Y.
  • Journal Title: Ophthalmologica Volume: 234 Pages: 139-150
  • DOI: 10.1159/000437360
  • Peer Reviewed
• [Journal Article] Resolution of exudative changes refractory to ranibizumab after aflibercept injections at the margin of inferior staphyloma in tilted disc syndrome. (2015)
  • Author(s): Hirano Y, Yasukawa T, Tsukada A, Yokoyama S, Ito Y, Nakazawa Y.
  • Journal Title: Ophthalmic Surg Lasers Imaging Retina Volume: 46 Pages: 384-386
  • DOI: 10.3928/23258160-20150323-16
  • Peer Reviewed
• [Journal Article] Short pulse laser induces less inflammatory cytokines in the murine retina after laser photocoagulation. (2015)
  • Author(s): Ito A, Hirano Y, Nozaki M, Ashikari M, Sugitani K, Ogura Y.
  • Journal Title: Ophthalmic Res Volume: 53 Pages: 65-73
  • DOI: 10.1159/000366520
  • Peer Reviewed
• [Journal Article] Vitrectomy without gas tamponade for macular retinoschisis associated with normal-tension glaucoma. (2015)
  • Author(s): Orazbekov L, Yasukawa T, Hirano Y, Ogura S, Usui H, Nozaki M, Ogura Y.
  • Journal Title: Ophthalmic Surg Lasers Imaging Retina Volume: 46 Pages: 107-110
  • DOI: 10.3928/23258160-20150101-21
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Intravitreal ranibizumab for patients with neovascular age-related macular degeneration with good baseline visual acuity (2015)
  • Author(s): Kato A, Yasukawa T, Suga K, Hirano Y, Nozaki M, Yoshida M, Ogura Y.
  • Journal Title: Ophthalmologica Volume: 233 Pages: 27-34
  • DOI: 10.1159/000368249
  • Peer Reviewed
• [Presentation] 網膜静脈分枝閉塞症に伴う黄斑浮腫に対するラニビズマブ硝子体内投与の12ヶ月成績 (2018)
  • Author(s): 安田優介、平野佳男、川村美穂子、高瀬範明、安川力、吉田宗徳、小椋祐一郎
  • Organizer: 第122回日本眼科学会総会
• [Presentation] 広角インドシアニングリーン蛍光眼底造影を用いた原田病の脈絡膜血管密度解析 (2017)
  • Author(s): 杉谷和彦、平野佳男、安川力、吉田宗徳、小椋祐一郎
  • Organizer: 第56回日本網膜硝子体学会総会
• [Presentation] 網膜静脈閉塞症患者における網膜無灌流領域の網膜感度と黄斑浮腫の関係 (2017)
  • Author(s): 富安胤太、平野佳男、鈴木識裕、江﨑雄也、安田優介、植村明嘉、安川力、吉田宗徳、小椋祐一郎
  • Organizer: 第71回日本臨床眼科学会
• [Presentation] 網膜静脈分枝閉塞症における毛細血管瘤の形態分類と網膜浮腫への関与 (2017)
  • Author(s): 江﨑雄也、平野佳男、鈴木識裕、富安胤太、安田優介、小椋祐一郎
  • Organizer: 第71回日本臨床眼科学会
• [Presentation] Retinal Sensitivity in Nonperfused Areas is Correlated with Macular Edema and Microaneurysms Formation in Eyes with Retinal Vein Occlusion (2017)
  • Author(s): Tomiyasu Taneto、Hirano Yoshio、Yoshida Munenori、Suzuki Norihiro、Uemura Akiyoshi、Yasukawa Tsutomu、Ogura Yuichiro
  • Organizer: 第42回日本微小循環学会
• [Presentation] 網膜静脈分枝閉塞症に伴う黄斑浮腫に対するラニビズマブ硝子体内投与の6ヶ月成績 (2017)
  • Author(s): 川村美穂子、平野佳男、吉田宗徳、水谷武史、杉谷和彦、小椋祐一郎
  • Organizer: 第121回日本眼科学会総会
• [Presentation] 網膜静脈閉塞症における網脈絡膜循環障害評価 (2017)
  • Author(s): 平野佳男
  • Organizer: 第121回日本眼科学会総会
  • Invited
• [Presentation] 広角蛍光眼底造影による網膜静脈分枝閉塞症の網膜周辺部b；窯変の評価と視力予後の関係 (2017)
  • Author(s): 安田優介、平野佳男、鈴木識裕、富安胤太、江﨑雄也、小椋祐一郎
  • Organizer: 第35回日本眼循環学会
• [Presentation] Six-Month Results of Ranibizumab for Macular Edema Following Branch Retinal Vein Occlusion -A Single-Center Prospective Study- (2017)
  • Author(s): Kawamura Mihoko、Hirano Yoshio、Yoshida Munenori、Mizutani Takeshi、Sugitani Kazuhiko、Ogura Yuichiro
  • Organizer: the 17th EURETINA Congress
  • Int'l Joint Research
• [Presentation] Densitometry of Choroidal Vessels in Eyes with Vogt-Koyanagi-Harada Disease by Wide-Field Indocyanine Green Angiography (2017)
  • Author(s): Kurobe Ryo、Sugitani Kazuhiko、Hirano Yoshio、Yasukawa Tsutomu、Ogura Yuichiro
  • Organizer: the 17th EURETINA Congress
  • Int'l Joint Research
• [Presentation] Retinal Sensitivity in Nonperfused Areas: Correlation with Macular Edema and Microaneurysm Formation in Retinal Vein Occlusion (2017)
  • Author(s): Hirano Yoshio、Yoshida Munenori、Ogura Yuichiro
  • Organizer: AAO2017
  • Int'l Joint Research
• [Book] 【網膜静脈閉塞症の最新のとらえ方】OCT angiographyによる虚血の評価. 眼科 (2017)
  • Author(s): 平野佳男、小椋祐一郎
  • Total Pages: 7
  • Publisher: 金原出版株式会社
• [Book] 【OCTで血管を斬る！】網膜静脈閉塞症(RVO). RETINA Medicine vol.6no.2(2017年秋号) (2017)
  • Author(s): 鈴木識裕、平野佳男
  • Total Pages: 6
  • Publisher: 先端医学社
• [Book] 眼循環 わかりやすい臨床口座 網膜静脈閉塞症と網膜循環障害. 日本の眼科 (2017)
  • Author(s): 平野佳男
  • Total Pages: 6
  • Publisher: 外為印刷
• [Book] 【光干渉断層血管撮影(OCT angiography)のすべて】光干渉断層血管撮影の網膜静脈閉塞症への応用. あたらしい眼科 (2017)
  • Author(s): 平野佳男
  • Total Pages: 5
  • Publisher: メデイカル出版
• [Book] 抗VEGF治療セミナー 抗VEGF療法後の眼内炎の1例. あたらしい眼科 (2017)
  • Author(s): 江﨑雄也、平野佳男
  • Total Pages: 2
  • Publisher: メデイカル出版
• [Book] 【新人スタッフのための めめ子と学ぶ！眼科のキーワード50これだけ】処置・手術のためのキーワード 角膜移植術. 眼科ケア (2017)
  • Author(s): 江﨑雄也、平野佳男
  • Total Pages: 2
  • Publisher: メデイカル出版