The role of YAP/TAZ in chroidal vascular structure and choroidal neovascularization

• Project/Area Number: 18K16926
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56060:Ophthalmology-related
• Research Institution: Kobe University
• Principal Investigator: Matsumiya Wataru 神戸大学, 医学研究科, 助教 (30707120)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: YAP/TAZ / pYAP / 脈絡膜新生血管 / 脈絡膜 / 脈絡膜血管内皮細胞 / ベルテポルフィン / YAP / 実験的脈絡膜血管新生 / 脈絡膜血管形態 / YAPTAZ / 血管新生 / ポリープ状脈絡膜血管症

Outline of Final Research Achievements

This study aims to clarify the role of the Hippo pathway effector YAP / TAZ in choroidal angiogenesis (CNV). In an experiment to see the effect of the YAP inhibitor, verteporfin (VP), using a laser-induced CNV model, the CNV volume was significantly smaller in VP treatment than in control. Thus, it was suggested that VP might suppress CNV progression by YAP inhibitory action. We also investigated the effect of VP on YAP in choroidal blood vessels using human choroidal vascular endothelial cells and found that as the VP concentration increased, the intranuclear transition of pYAP was suppressed. The above suggests that YAP may play an important role in choroidal blood vessels.

Academic Significance and Societal Importance of the Research Achievements

近年、加齢黄斑変性(AMD)の一亜型であるポリープ状脈絡膜血管症（PCV）の治療において、YAP阻害作用を持つベルテポルフィンを用いた光線力学療法の有効性が臨床的に注目されている。本研究では、AMDの病態の首座である脈絡膜血管においてYAPが重要な役割を担っている可能性が示唆された。本研究の結果が、今後、YAPを介するHippo経路をターゲットにしたAMD及びPCV治療の臨床応用につながる可能性が期待される。

Research Products

• [Journal Article] Changes in choroidal imaging parameters following adalimumab therapy for refractory noninfectious uveitis (2021)
  • Author(s): Nishisho Ryuto、Kusuhara Sentaro、Sotani Noriyuki、Kim Kyong Woo、Katsuyama-Yoshikawa Atsuko、Matsumiya Wataru、Akashi Kengo、Morinobu Akio、Nakamura Makoto
  • Journal Title: Graefe's Archive for Clinical and Experimental Ophthalmology Volume: 259 Issue: 5 Pages: 1273-1280
  • DOI: 10.1007/s00417-020-05032-9
  • NAID: 120007038637
  • Peer Reviewed
• [Journal Article] A case of panuveitis and retinal vasculitis associated with pembrolizumab therapy for metastatic lung cancer (2021)
  • Author(s): Kim Kyung Woo、Kusuhara Sentaro、Tachihara Motoko、Mimura Chihiro、Matsumiya Wataru、Nakamura Makoto
  • Journal Title: American Journal of Ophthalmology Case Reports Volume: 22 Pages: 101072-101072
  • DOI: 10.1016/j.ajoc.2021.101072
  • Peer Reviewed / Open Access
• [Journal Article] Factors associated with the development of ocular candidiasis and ocular prognosis with echinocandin therapy for candidemia (2021)
  • Author(s): Sakai Daiki、Matsumiya Wataru、Kusuhara Sentaro、Nakamura Makoto
  • Journal Title: Journal of Ophthalmic Inflammation and Infection Volume: 11 Issue: 1
  • DOI: 10.1186/s12348-021-00248-0
  • NAID: 120007097075
  • Peer Reviewed / Open Access
• [Journal Article] Structural changes of corneal epithelium in belantamab-associated superficial keratopathy using anterior segment optical coherence tomography (2021)
  • Author(s): Matsumiya Wataru、Karaca Irmak、Ghoraba Hashem、Akhavanrezayat Amir、Mobasserian Azadeh、Hassan Muhammad、Regenold Jonathan、Yasar Cigdem、Liedtke Michaela、Kitazawa Koji、Nguyen Quan Dong
  • Journal Title: American Journal of Ophthalmology Case Reports Volume: 23 Pages: 101133-101133
  • DOI: 10.1016/j.ajoc.2021.101133
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Outcomes of Primary 27-Gauge Vitrectomy for 73 Consecutive Cases With Uveitis-Associated Vitreoretinal Disorders (2021)
  • Author(s): Kim Kyung Woo、Kusuhara Sentaro、Imai Hisanori、Sotani Noriyuki、Nishisho Ryuto、Matsumiya Wataru、Nakamura Makoto
  • Journal Title: Frontiers in Medicine Volume: 8
  • DOI: 10.3389/fmed.2021.755816
  • NAID: 120007170800
• [Journal Article] Unilateral acute anterior uveitis with macular edema following the use of sildenafil citrate in a patient with HLA-B27 positivity (2021)
  • Author(s): Regenold Jonathan、Ghoraba Hashem、Akhavanrezayat Amir、Matsumiya Wataru、Mobasserian Azadeh、Karaca Irmak、Zaidi Moosa、Pham Brandon、Nguyen Quan Dong
  • Journal Title: American Journal of Ophthalmology Case Reports Volume: 24 Pages: 101228-101228
  • DOI: 10.1016/j.ajoc.2021.101228
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Changes in Gene Expression Profiling and Phenotype in Aged Multidrug Resistance Protein 4-Deficient Mouse Retinas (2021)
  • Author(s): Kim KW, Kusuhara S, Katsuyama-Yoshikawa A, Nobuyoshi S, Kitamura M, Mori S, Sotani N, Ueda K, Matsumiya W, Miki A, Kurimoto T, Imai H, Nakamura M.
  • Journal Title: Antioxidants (Basel) Volume: 15 Issue: 3 Pages: 455-455
  • DOI: 10.3390/antiox10030455
  • NAID: 120007006644
  • Peer Reviewed / Open Access
• [Journal Article] The choroidal structure changes in a case with hypertensive choroidopathy (2020)
  • Author(s): Daiki Sakai, Wataru Matsumiya, Sentaro Kusuhara, Makoto Nakamura
  • Journal Title: Am J Ophthalmol Case Rep. Volume: 18 Pages: 100710-100710
  • DOI: 10.1016/j.ajoc.2020.100710
  • Peer Reviewed / Open Access
• [Journal Article] Severe vision loss secondary to retinal arteriolar occlusions after multiple intravitreal brolucizumab administrations. (2020)
  • Author(s): Jain A, Chea S, Matsumiya W, Halim MS, Yaşar Ç, Kuang G, Sepah YJ, Khanani AM, Do DV, Nguyen QD.
  • Journal Title: Am J Ophthalmol Case Rep. Volume: 18 Pages: 100687-100687
  • DOI: 10.1016/j.ajoc.2020.100687
  • Peer Reviewed / Open Access
• [Journal Article] Association of an age-related maculopathy susceptibility 2 gene variant with the 12-month outcomes of intravitreal aflibercept combined with photodynamic therapy for polypoidal choroidal vasculopathy. (2019)
  • Author(s): Nakai S, Matsumiya W, Miki A, Honda S, Nakamura M.
  • Journal Title: Jpn J Ophthalmol. Volume: 63 Issue: 5 Pages: 389-395
  • DOI: 10.1007/s10384-019-00683-6
  • Peer Reviewed
• [Presentation] OCTを用いた炎症細胞の評価と応用 (2021)
  • Author(s): 松宮 亘
  • Organizer: 第125回 日本眼科学会
  • Invited
• [Presentation] Association of oral montelukast with reduced odds of developing neovascular age-related macular degeneration (2021)
  • Author(s): Irmak Karaca, Wataru Matsumiya, Amir Akhavanrezayat, Gunay Uludag, Cigdem Yasar, Hashem Ghoraba, Azadeh Mobasserian, Jonathan Regenold, Brandon Huy Pham, Rubbia Afridi, Muhammad Sohail Halim, Diana V. Do, Yasir J. Sepah, Quan Dong Nguyen,
  • Organizer: ARVO2021
• [Presentation] Factors associated with the development of ocular candidiasis and ocular prognosis with echinocandin therapy for candidemia (2021)
  • Author(s): Daiki Sakai, Wataru Matsumiya , Sentaro Kusuhara, Makoto Nakamura
  • Organizer: ARVO2021
• [Presentation] Correlation between photoreceptor density in adaptive optics imaging with retinal structure and sensitivity in autoimmune retinopathy (2021)
  • Author(s): Wataru Matsumiya, Amir Akhavanrezayat, Gunay Uludag, Cigdem Yasar, Hashem Ghoraba, Azadeh Mobasserian, Irmak Karaca, Brandon Pham, Jaclyn Joyce Hwang, Rubbia Afridi, Muhammad Sohail Halim, Diana V. Do, Yasir J. Sepah, Quan Dong Nguyen
  • Organizer: ARVO2021
• [Presentation] Photoreceptor Density in Adaptive Optics Imaging Is Correlated With Retinal Structure and Sensitivity in Autoimmune Retinopathy (2021)
  • Author(s): Wataru Matsumiya, Amir Akhavanrezayat, Gunay Uludag, Cigdem Yasar, Hashem Ghoraba, Azadeh Mobasserian, Irmak Karaca, Jonathan Regenold, Brandon Pham, Muhammad Sohail Halim, Diana V. Do, Yasir J. Sepah, Quan Dong Nguyen
  • Organizer: American Academy of Ophthalmology(AAO)2021
• [Presentation] Association of Oral Montelukast with Reduced Odds of Developing Neovascular Age-related Macular Degeneration (2021)
  • Author(s): Wataru Matsumiya
  • Organizer: 2021 Virtual Meeting of the International Ocular Inflammation Society
  • Invited
• [Presentation] Multimodal imaging in posterior segment inflammation (2021)
  • Author(s): Wataru Matsumiya
  • Organizer: Muscat International Ophthalmology Conference 2021
  • Invited
• [Presentation] Vogt-小柳-原田病治療経過中の脈絡膜再肥厚と脈絡膜構造変化の検討 (2019)
  • Author(s): 松宮亘、西庄龍東、勝山敦子、宇治彰人（京都大）、楠原仙太郎、中村誠
  • Organizer: 日本眼科学会総会
• [Presentation] ポリープ状脈絡膜血管症へのaflibercept併用光線力学的療法と異常血管網の進展 (2019)
  • Author(s): 中井 駿一朗、松宮 亘、林田 真由香、三木 明子、本田 茂、中村 誠
  • Organizer: 日本眼科学会総会
• [Presentation] Vogt-小柳-原田病治療前後の脈絡膜構造指標の変化と相関 (2019)
  • Author(s): 西庄龍東、松宮亘、勝山敦子、宇治彰人、楠原仙太郎、中村誠
  • Organizer: 日本眼科学会総会
• [Presentation] The relationship between the choroidal structure and choroidal thickening in Vogt-Koyanagi-Harada disease (2019)
  • Author(s): Wataru Matsumiya, Ryuto Nishisho, Atsuko Katsuyama, Akihito Uji (Kyoto Univ.), Sentaro Kusuhara, Makoto Nakamura
  • Organizer: ARVO (Association for Research in Vision and Ophthalmology) 2019
• [Presentation] Post-treatment change of choroidal structural parameters and their correlations and fluctuations in Vogt-Koyanagi-Harada disease (2019)
  • Author(s): Ryuto Nishisho, Wataru Matsumiya, Atsuko Katsuyama, Akihito Uji (Kyoto Univ.), Sentaro Kusuhara, Makoto Nakamura
  • Organizer: ARVO (Association for Research in Vision and Ophthalmology) 2019
• [Presentation] The association of the branching vascular network area progression with the outcomes of combination therapy with intravitreal aflibercept and verteporfin photodynamic therapy for polypoidal choroidal vasculopathy (2019)
  • Author(s): Shunichiro Nakai, Wataru Matsumiya, Mayuka Hayashida, Akiko Miki, Shigeru Honda (Osaka City University), Makoto Nakamura
  • Organizer: ARVO (Association for Research in Vision and Ophthalmology) 2019
• [Presentation] Wataru Matsumiya, Mayuka Hayashida, Ryuto Nishisyo, Akira Tetsumoto, Atsuko Katsuyama, Akiko Miki, Hisanori Imai, Sentaro Kusuhara, Makoto Nakamura (2019)
  • Author(s): Wataru Matsumiya, Mayuka Hayashida, Ryuto Nishisyo, Akira Tetsumoto, Atsuko Katsuyama, Akiko Miki, Hisanori Imai, Sentaro Kusuhara, Makoto Nakamura
  • Organizer: GOIW (Global Ocular Inflammation Workshops) 2019
• [Presentation] 経過中に脈絡膜変化を伴った妊娠高血圧症候群に続発した高血圧性脈絡膜症の1症例 (2019)
  • Author(s): 酒井 大輝、松宮 亘、楠原 仙太郎、中村 誠
  • Organizer: 第58回日本網膜硝子体学会総会
• [Presentation] ポリープ状脈絡膜血管症へのaflibercept単独療法とaflibercept併用光線力学的療法との2年経過比較 (2018)
  • Author(s): 中井 駿一朗、松宮 亘、本田 茂、林田 真由香、三木 明子、安積 淳、中村 誠
  • Organizer: 第57回網膜硝子体学会
• [Presentation] ポリープ状脈絡膜血管症へのアフリベルセプト併用光線力学療法後の網膜色素上皮萎縮 (2018)
  • Author(s): 松宮亘、本田茂、林田真由香、中井駿一朗、勝山敦子、大塚慶子、三木明子、楠原仙太郎、中村誠
  • Organizer: 第122回 日本眼科学会
• [Presentation] ポリープ状脈絡膜血管症に対するaflibercept併用光線力学的療法の3年経過 (2018)
  • Author(s): 中井 駿一朗、松宮 亘、本田 茂、林田 真由香、三木 明子、中村 誠
  • Organizer: 第72回 日本臨床眼科学会
• [Book] あたらしい眼科 (2019)
  • Author(s): 松宮 亘
  • Total Pages: 2
  • Publisher: メディカル葵出版