AMDマウスモデルの交感神経の脈絡膜新生血管及びマクロファージ眼内浸潤への関与

• Project/Area Number: 21K16893
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56060:Ophthalmology-related
• Research Institution: The University of Tokyo
• Principal Investigator: 東 惠子 東京大学, 医学部附属病院, 助教 (50772084)
• Project Period (FY): 2021-04-01 – 2026-03-31
• Project Status: Granted (Fiscal Year 2023)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2025: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000); Fiscal Year 2024: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2023: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2022: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2021: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: pachychoroid関連疾患 / PNV / CSC / 炎症性サイトカイン / 画像解析 / 抗VEGF薬 / 滲出型加齢黄斑変性 / 加齢黄斑変性 / 炎症サイトカイン / 骨髄交感神経受容体β3ブロッカー / レーザー誘発新生血管 / 脈絡膜新生血管

Outline of Research at the Start

研究代表者は、これまでに確立してきた加齢黄斑変性の脈絡膜新生血管に対する研究の学 術・技術基盤をもとに(1) 脈絡膜血管新生動物モデルを用いた本研究により、脈絡膜新生血 管の形成に関与する炎症細胞を特定する。さらに、(2) 脾臓交感神経除去または骨髄交感神 経遮断による脈絡膜新生血管や炎症細胞の眼内浸潤の変化を明らかにする。そして、(3) 得 られた標的分子の機能を用いて、これまでに検討されていなかった眼薬理動態における自律 神経の役割の検討を行う。

Outline of Annual Research Achievements

滲出型加齢黄斑変性は、昨今アジアを中心に頻繁に報告されている、pachychoroid関連疾患に基づいた虚血による新生血管発生機序が唱えられてきている。 炎症サイトカインに基づく機序または交感神経の血管新生への作用の検討とは別に、臨床でも画像解析を用いてpachychoroidによる虚血が加齢黄斑変性に与える影響を解析・数値化し、これを検討・発表・論文化することができた。本研究で得られた知見は、新たな病態概念を元に滲出型加齢黄斑変性の予後予測因子を新たに明らかとしたものであり、臨床所見や病態に基づいた個別化医療の確立の土台となる基盤的な研究と考えられる。
また、抗VEGF薬の種類も増え、治療の選択肢も増えてきている。そのため、どの抗VEGF薬がどのような特徴をもち、効果に差異があるのかなど特徴つける必要がある。この点の関しても引き続き今後も基礎・臨床の両方面から検討していく予定である。
昨年度同様、Multimodal imagingを用いて多数の画像診断機器を応用し、眼所見を多角的に評価する画像診断技法を用いた。結果を解析・数値化し、これを検討・発表・論文化を進めている。また抗VEGF薬と炎症サイトカインとの関連についても検討、共著として論文化した。
研究は概ね順調に進行しており、論文化も順調に進行していると考える。コロナ禍もようやく落ち着いたので、R5年は欧米での発表も可能となった。今後も積極的に海外発信していきたい。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

昨年度同様、Multimodal imagingを用いて多数の画像診断機器を応用し、眼所見を多角的に評価する画像診断技法を用いた。結果を解析・数値化し、これを検討・発表・論文化を進めている。また抗VEGF薬と炎症サイトカインとの関連についても検討、共著として論文化した。

Strategy for Future Research Activity

今後も基礎の結果を基盤にして、臨床での応用が可能かどうか、マルチモーダルイメージングを用いて実臨床での検討・解析を継続していく予定である。

Research Products

• [Journal Article] Effects of Progesterone and Other Gonadal Hormones on Glutamatergic Circuits in the Retina (2023)
  • Author(s): Ohkuma Mahito、Maruyama Takuma、Ishii Toshiyuki、Igarashi Nozomi、Azuma Keiko、Inoue Tatsuya、Obata Ryo、Miyachi Ei-ichi、Kaneda Makoto
  • Journal Title: Journal of Nippon Medical School Volume: 90 Issue: 4 Pages: 333-345
  • DOI: 10.1272/jnms.JNMS.2023_90-405
  • ISSN: 1345-4676, 1347-3409
  • Year and Date: 2023-08-25
  • Peer Reviewed
• [Journal Article] Cytokine profiles in the aqueous humor following brolucizumab administration for exudative age-related macular degeneration (2023)
  • Author(s): Terao Ryo、Obata Ryo、Okubo Atsushi、Aoki Shuichiro、Azuma Keiko、Ahmed Tazbir、Inoda Satoru、Hashimoto Yuto、Takahashi Ryota、Yoshida Hana、Misawa Manami、Takahashi Hironori、Takahashi Hidenori
  • Journal Title: Graefe's Archive for Clinical and Experimental Ophthalmology Volume: 261 Issue: 9 Pages: 2465-2476
  • DOI: 10.1007/s00417-023-06038-9
  • Peer Reviewed
• [Journal Article] Long-term visual outcomes in pachychoroid spectrum diseases and its associating factors of eyes with chronic central serous chorioretinopathy (2023)
  • Author(s): Azuma Keiko、Tanaka Nobuya、Aoki Shuichiro、Kitamoto Kohdai、Ueda Kohei、Inoue Tatsuya、Obata Ryo
  • Journal Title: Scientific Reports Volume: 13 Issue: 1 Pages: 1-11
  • DOI: 10.1038/s41598-023-49153-7
• [Journal Article] Investigating the clinical validity of the guided progression analysis definition with 10?2 visual field in retinitis pigmentosa (2023)
  • Author(s): Asano Shotaro、Asaoka Ryo、Oishi Akio、Fujino Yuri、Murata Hiroshi、Azuma Keiko、Miyata Manabu、Obata Ryo、Inoue Tatsuya
  • Journal Title: PLOS ONE Volume: 18 Issue: 9 Pages: 1-11
  • DOI: 10.1371/journal.pone.0291208
  • Peer Reviewed / Open Access
• [Journal Article] Longitudinal anatomical and visual outcome of macular telangiectasia type 2 in Asian patients (2023)
  • Author(s): Totsuka Kiyoto、Aoki Shuichiro、Arai Takahiro、Kitamoto Kodai、Azuma Keiko、Fujino Ryosuke、Inoue Tatsuya、Obata Ryo
  • Journal Title: Scientific Reports Volume: 13 Issue: 1 Pages: 1-11
  • DOI: 10.1038/s41598-023-46394-4
• [Journal Article] Intravenous lipo-prostaglandin E1 administration for patients with acute central retinal artery occlusion (2022)
  • Author(s): Suzuki Takafumi、Obata Ryo、Inoue Tatsuya、Ueta Yoshiki、Azuma Keiko、Tate Hideo、Kitamoto Kohdai、Otaki Chisato、Hashimoto Yoshihiro、Aihara Makoto、Tachi Naoko
  • Journal Title: BMJ Open Ophthalmology Volume: 7 Issue: 1 Pages: e001014-e001014
  • DOI: 10.1136/bmjophth-2022-001014
• [Journal Article] Relationship between visual acuity and visual field and its reproducibility in patients with retinitis pigmentosa (2022)
  • Author(s): Asaoka Ryo、Miyata Manabu、Oishi Akio、Fujino Yuri、Murata Hiroshi、Azuma Keiko、Obata Ryo、Inoue Tatsuya
  • Journal Title: Eye Volume: 02043 Issue: 6 Pages: 0-0
  • DOI: 10.1038/s41433-022-02043-0
  • Peer Reviewed
• [Journal Article] LOCATIONAL AGREEMENT OF NEAR-INFRARED AUTOFLUORESCENCE WITH CHOROIDAL VASCULAR HYPERPERMEABILITY IN CENTRAL SEROUS CHORIORETINOPATHY (2022)
  • Author(s): Azuma Keiko、Nomura Yoko、Kitamoto Kohdai、Hashimoto Yohei、Fujino Ryosuke、Ueda Kohei、Inoue Tatsuya、Obata Ryo
  • Journal Title: Retina Volume: 42 Issue: 11 Pages: 2203-2209
  • DOI: 10.1097/iae.0000000000003593
  • Peer Reviewed
• [Journal Article] Association between retinal sensitivity and the presence of quiescent choroidal neovascularization in pachychoroid diseases (2022)
  • Author(s): Ozawa Rion、Azuma Keiko、Nomura Yoko、Murata Hiroshi、Asaoka Ryo、Kitamoto Kohdai、Ueda Kohei、Inoue Tatsuya、Obata Ryo
  • Journal Title: PLOS ONE Volume: 17 Issue: 7 Pages: 1543-1548
  • DOI: 10.1371/journal.pone.0271543
  • Peer Reviewed / Open Access
• [Journal Article] Relationship between the vessel density around the optic nerve head and visual field deterioration in eyes with retinitis pigmentosa (2022)
  • Author(s): Nakajima Kosuke、Inoue Tatsuya、Maruyama-Inoue Maiko、Yanagi Yasuo、Kadonosono Kazuaki、Ogawa Asako、Hashimoto Yohei、Azuma Keiko、Terao Ryo、Asaoka Ryo、Obata Ryo
  • Journal Title: Graefe's Archive for Clinical and Experimental Ophthalmology Volume: 260 Issue: 4 Pages: 1097-1103
  • DOI: 10.1007/s00417-021-05288-9
• [Journal Article] Retinal pigment epithelium melanin distribution estimated by polarisation entropy and its association with retinal sensitivity in patients with high myopia (2022)
  • Author(s): Harimoto Akira、Obata Ryo、Yamamoto Motoshi、Aoki Nobuyori、Yamanari Masahiro、Sugiyama Satoshi、Kitano Marie、Fujita Asahi、Minami Takahiro、Ueda Kohei、Azuma Keiko、Inoue Tatsuya、Aihara Makoto、Kato Satoshi
  • Journal Title: British Journal of Ophthalmology Volume: 106 Issue: 10 Pages: 1457-1462
  • DOI: 10.1136/bjophthalmol-2021-318890
• [Journal Article] Deep learning-assisted (automatic) diagnosis of glaucoma using a smartphone (2021)
  • Author(s): Nakahara Kenichi、Asaoka Ryo、Tanito Masaki、Shibata Naoto、Mitsuhashi Keita、Fujino Yuri、Matsuura Masato、Inoue Tatsuya、Azuma Keiko、Obata Ryo、Murata Hiroshi
  • Journal Title: British Journal of Ophthalmology Volume: 106 Issue: 4 Pages: 587-592
  • DOI: 10.1136/bjophthalmol-2020-318107
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Assessment of the choroidal structure in pregnant women in the first trimester (2021)
  • Author(s): Azuma K, Okubo A, Suzuki T, Igarashi N, Nomura Y, Soga H, Murata H, Fujino R, Ogawa A, Matsui H, Nagamatsu T, Iriyama T, Asaoka R, Inoue T, Maruyama-Inoue M, Kadonosono K, Obata R.
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 4629-4629
  • DOI: 10.1038/s41598-021-84204-x
  • Peer Reviewed / Open Access
• [Journal Article] Association between serum soluble fms-like tyrosine kinase-1 and the central choroidal thickness during pregnancy: a prospective study (2021)
  • Author(s): Suzuki Takafumi、Inoue Tatsuya、Igarashi Nozomi、Agata Chisato、Okubo Atsushi、Nagamatsu Takeshi、Iriyama Takayuki、Maruyama-Inoue Maiko、Yanagi Yasuo、Kadonosono Kazuaki、Asaoka Ryo、Azuma Keiko、Obata Ryo
  • Journal Title: BMJ Open Ophthalmology Volume: 6 Issue: 1 Pages: e000888-e000888
  • DOI: 10.1136/bmjophth-2021-000888
  • Peer Reviewed
• [Journal Article] Association between the number of visual fields and the accuracy of future prediction in eyes with retinitis pigmentosa (2021)
  • Author(s): Asaoka Ryo、Oishi Akio、Fujino Yuri、Murata Hiroshi、Azuma Keiko、Miyata Manabu、Obata Ryo、Inoue Tatsuya
  • Journal Title: BMJ Open Ophthalmology Volume: 6 Issue: 1 Pages: e000900-e000900
  • DOI: 10.1136/bmjophth-2021-000900
  • Peer Reviewed
• [Journal Article] Association of Near-Infrared and Short-Wavelength Autofluorescence With the Retinal Sensitivity in Eyes With Resolved Central Serous Chorioretinopathy (2021)
  • Author(s): Soga Hirotsugu、Asaoka Ryo、Kadonosono Kazuaki、Maruyama-Inoue Maiko、Igarashi Nozomi、Kitano Marie、Kitamoto Kohdai、Azuma Keiko、Obata Ryo、Inoue Tatsuya
  • Journal Title: Investigative Opthalmology & visual science Volume: 62 Issue: 3 Pages: 36-36
  • DOI: 10.1167/iovs.62.3.36
  • Peer Reviewed
• [Journal Article] Assessment of macular function in patients with non-vascularized pigment epithelial detachment (2021)
  • Author(s): Kitano Marie、Fujita Asahi、Asaoka Ryo、Inoue Tatsuya、Amari Tatsuaki、Komatsu Kayoko、Yamamoto Motoshi、Ogawa Asako、Aoki Nobuyori、Yamanari Masahiro、Sugiyama Satoshi、Aihara Makoto、Kato Satoshi、Azuma Keiko、Maruyama-Inoue Maiko、Kadonosono Kazuaki、Obata Ryo
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 16577-16577
  • DOI: 10.1038/s41598-021-96151-8
  • Peer Reviewed
• [Journal Article] Clinical features of cases with retinal pigment epithelium aperture (2021)
  • Author(s): Yoshinaga Akie、Ueda Kohei、Terao Ryo、Azuma Keiko、Inoue Tatsuya、Obata Ryo
  • Journal Title: American Journal of Ophthalmology Case Reports Volume: 22 Pages: 101083-101083
  • DOI: 10.1016/j.ajoc.2021.101083
  • Peer Reviewed
• [Journal Article] Three-Dimensional Distribution Of Fundus Depolarization and Associating Factors Measured Using Polarization-Sensitive Optical Coherence Tomography (2021)
  • Author(s): Fujita Asahi、Amari Tatsuaki、Ueda Kohei、Azuma Keiko、Inoue Tatsuya、Komatsu Kayoko、Yamamoto Motoshi、Aoki Nobuyori、Yamanari Masahiro、Sugiyama Satoshi、Aihara Makoto、Kato Satoshi、Obata Ryo
  • Journal Title: Translational Vision Science & technology Volume: 10 Issue: 2 Pages: 30-30
  • DOI: 10.1167/tvst.10.2.30
  • Peer Reviewed
• [Journal Article] Correlation between choroidal structure and smoking in eyes with central serous chorioretinopathy (2021)
  • Author(s): Okawa Kazuyoshi、Inoue Tatsuya、Asaoka Ryo、Azuma Keiko、Obata Ryo、Arasaki Rei、Ikeda Shouko、Ito Arisa、Maruyama-Inoue Maiko、Yanagi Yasuo、Kadonosono Kazuaki
  • Journal Title: PLOS ONE Volume: 16 Issue: 3 Pages: 0249073-0249073
  • DOI: 10.1371/journal.pone.0249073
  • Peer Reviewed
• [Journal Article] Detecting Progression of Retinitis Pigmentosa Using the Binomial Pointwise Linear Regression Method (2021)
  • Author(s): Asano Shotaro、Oishi Akio、Asaoka Ryo、Fujino Yuri、Murata Hiroshi、Azuma Keiko、Miyata Manabu、Obata Ryo、Inoue Tatsuya
  • Journal Title: Translational Vision Science & Technology Volume: 10 Issue: 13 Pages: 15-15
  • DOI: 10.1167/tvst.10.13.15
  • Peer Reviewed
• [Journal Article] Correlation between fundus autofluorescence and visual function in patients with cone-rod dystrophy (2021)
  • Author(s): Kanda Satoru、Hara Takumi、Fujino Ryosuke、Azuma Keiko、Soga Hirotsugu、Asaoka Ryo、Obata Ryo、Inoue Tatsuya
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 1911-1911
  • DOI: 10.1038/s41598-021-81597-7
  • Peer Reviewed
• [Journal Article] Development and validation of a visual field cluster in retinitis pigmentosa (2021)
  • Author(s): Omoto Takashi、Oishi Akio、Asaoka Ryo、Fujino Yuri、Murata Hiroshi、Azuma Keiko、Miyata Manabu、Obata Ryo、Inoue Tatsuya
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 9671-9671
  • DOI: 10.1038/s41598-021-89233-0
  • Peer Reviewed / Open Access
• [Journal Article] Imaging of a retinal pigment epithelium aperture using polarization-sensitive optical coherence tomography (2021)
  • Author(s): Obata Ryo、Yoshinaga Akie、Yamamoto Motoshi、Komatsu Kayoko、Aoki Nobuyori、Yamanari Masahiro、Sugiyama Satoshi、Minami Takahiro、Azuma Keiko、Inoue Tatsuya、Aihara Makoto、Kato Satoshi
  • Journal Title: Japanese Journal of Ophthalmology Volume: 65 Issue: 1 Pages: 30-41
  • DOI: 10.1007/s10384-020-00787-4
  • NAID: 210000171778
  • Peer Reviewed
• [Journal Article] OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY STUDY OF CHOROIDAL NEOVASCULARIZATION ASSOCIATED WITH EARLY-ONSET DRUSEN (2019)
  • Author(s): Terao Ryo、Matsuda Aya、Ogawa Asako、Shimizu Kimiko、Azuma Keiko、Inoue Tatsuya、Obata Ryo
  • Journal Title: Retinal Cases & Brief Reports Volume: - Issue: 5 Pages: 1-1
  • DOI: 10.1097/icb.0000000000000856
  • Peer Reviewed
• [Presentation] Pachychoroid関連疾患群の長期視力予後比較 (2023)
  • Author(s): 東 惠子1, 田中 伸弥1, 青木 修一郎1, 北本 昂大1, 上田 浩平1, 井上 達也1,2 , 小畑 亮1
  • Organizer: 第 127 回日本眼科学会総会
• [Presentation] 網膜色素上皮裂孔におけるメラニン分布および網膜感度の変化 (2023)
  • Author(s): 東 惠子 1) 、 山藤 大輔 2) 、 杉山 聡 2) 、 青木 伸頼 2) 、 一瀬 才甫 2) 、 青木 修一郎 1) 、 北本 昴大 1) 、 井上 達也 1) 3) 、 小畑 亮 1)
  • Organizer: 第62回日本網膜硝子体学会総会
• [Presentation] Long-term visual outcomes of pachychoroid spectrum diseases (2023)
  • Author(s): Keiko Azuma MD, PhD1; Nobuya Tanaka MD1; Shuichiro Aoki MD1; Kohdai Kitamoto MD, PhD1; Kohei Ueda MD1; Tatsuya Inoue MD, PhD2 & Ryo Obata MD, PhD1*
  • Organizer: 23rd Euretina Congress Certificate of Attendance
• [Presentation] Locational agreement of near-infrared autofluorescence with choroidal vascular hyperpermeability in central serous chorioretinopathy (2022)
  • Author(s): 東惠子
  • Organizer: 臨床眼科学会