Macrophage targeted new treatment for ocular inflammation

• Project/Area Number: 23592613
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Tohoku University (2012-2013); Kyoto Prefectural University of Medicine (2011)
• Principal Investigator: MARUYAMA Kazuichi 東北大学, 大学病院, 講師 (10433244)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: アポトーシス / マクロファージ / リンパ管 / 炎症 / リンパ管新生 / 角膜移植

Research Abstract

The small weight chemical compound could suppress inflamed cytokine from C57/BL6 or ICR mice macrophage that was stimulated with LPS and interferon gamma. Especially, TNF-alpha secretion from macrophage that was stimulated with LPS and interferon gamma was dramatically suppress by this small weight chemical compound. The purpose of this experiment, we would like to use this small weight chemical compound as local treatment such as eye drop. However, this small weight chemical compound induced inflammation in the eye, especially corneal epithelium. In order to chemical induced local inflammation, we decided to use this small weight chemical compound as systemic administration. As a result, this small weight chemical compound could suppress lymphangiogenesis in corneal suture placement experiment.

Research Products

• [Journal Article] The VEGF-C/VEGFR3 signaling pathway contributes to resolving chronic skin inflammation by activating lymphatic vessel function (2014)
  • Author(s): Hagura A, Asai J, Maruyama K, Takenaka H, Kinoshita S, Katoh N
  • Journal Title: J Dermatol Sci Volume: 73(2) Pages: 1135-41
  • Peer Reviewed
• [Journal Article] LRIG1 inhibits STAT3-dependent inflammation to maintain corneal homeostasis (2014)
  • Author(s): Nakamura T, Hamuro J, Takaishi M, Simmons S, Maruyama K, Zaffalon A, Bentley AJ, Kawasaki S, Nagata-Takaoka M, Fullwood NJ, Itami S, Sano S, Ishii M, Barrandon Y, Kinoshita S
  • Journal Title: J Clin Invest Volume: 124(1) Pages: 385-97
  • Peer Reviewed
• [Journal Article] Age Differences in Sarcoidosis Patients with Posterior Ocular Lesions (2013)
  • Author(s): Nagata K, Maruyama K, Sugita S, Fukuchi U, Terada Y, Ishizuka A, Nakazawa T, Mochizuki M, Kinoshita S
  • Journal Title: Ocul Immunol Inflamm Volume: (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Critical role of Nrf2 in oxidative stress-induced retinal ganglion cell death (2013)
  • Author(s): Himori N, Yamamoto K, Maruyama K, Ryu M, Taguchi K, Yamamoto M, Nakazawa T
  • Journal Title: J Neurochem Volume: 127(5) Pages: 669-80
  • Peer Reviewed
• [Journal Article] Waveform analysis of ocular blood flow and the early detection of normal tension glaucoma (2013)
  • Author(s): Shiga Y, Omodaka K, Kunikata H, Ryu M, Yokoyama Y, Tsuda S, Asano T, Maekawa S, Maruyama K, Nakazawa T
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 54(12) Pages: 7699-706
  • Peer Reviewed
• [Journal Article] Intraocular Invasion of Adult T-Cell Leukemia Cells without Systemic Symptoms after Cataract Surgery (2013)
  • Author(s): Maruyama K, Nagata K, Kojima K, Inaba T, Sugita S, Mochizuki M, Kinoshita S
  • Journal Title: Case Report in Ophthalmology Volume: 4(3) Pages: 252-6
  • Peer Reviewed
• [Journal Article] Simulated Visual Field Produced from Macular RNFLT Data in Patient with Glaucoma (2013)
  • Author(s): Takahashi M, Omodaka K, Maruyama K, Yamaguchi T, Himori N, Shiga Y, Ryu M, Kunikata H, Nakazawa T
  • Journal Title: Current Eye Research Volume: 38(11) Pages: 1133-41
  • Peer Reviewed
• [Journal Article] Use of a Comprehensive Polymerase Chain Reaction System for Diagnosis of Ocular Infectious Diseases (2013)
  • Author(s): Sugita S, Ogawa M, Shimizu N, Morio T, Ohguro N, Nakai K, Maruyama K, Nagata K, Takeda A, Usui Y, Sonoda KH, Takeuchi M, Mochizuki M
  • Journal Title: Ophthalmology Volume: 120(9) Pages: 1761-8
  • Peer Reviewed
• [Journal Article] Development of a new strategy of visual field test for macular dysfunction in patients with open angle glaucoma (2013)
  • Author(s): Omodaka K, Kunimatsu S, Ryu M, Shiga Y, Tsuda S, Yokoyama Y, Watanabe R, Takahashi H, Maruyama K, Kunikata H, Nakazawa T
  • Journal Title: Jpn J Ophthalmol Volume: 57(5) Pages: 457-62
  • NAID: 10031201478
  • Peer Reviewed
• [Journal Article] Novel anti(lymph)angiogenic treatment strategies for corneal and ocular surface diseases (2013)
  • Author(s): Bock F, Maruyama K, Regenfuss B, Hos D, Steven P, Heindl LM, Cursiefen C
  • Journal Title: Prog Retin Eye Res Volume: 34 Pages: 89-112
  • Peer Reviewed
• [Journal Article] EphrinB2-EphB4 Signals Regulate Formation and Maintenance of Funnel-Shaped Valves in Corneal Lymphatic Capillaries (2013)
  • Author(s): Katsuta H, Fukushima Y, Maruyama K, Hirashima M, Nishida K, Nishikawa S, Uemura A
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 54(6) Pages: 4102-8
  • Peer Reviewed
• [Journal Article] Deletion of Tetraspanin CD9 Diminishes Lymphangiogenesis in Vivo and in Vitro (2013)
  • Author(s): Iwasaki T, Takeda Y, Maruyama K, Yokosaki Y, Tsujino K, Tetsumoto S, Kuhara H, Nakanishi K, Otani Y, Jin Y, Kohmo S, Hirata H, Takahashi R, Suzuki M, Inoue K, Nagatomo I, Goya S, Kijima T, Kumagai T, Tachibana I, Kawase I, Kumanogoh A
  • Journal Title: J Biol Chem Volume: 288(4) Pages: 2118-31
  • Peer Reviewed
• [Journal Article] Novel anti(lymph)angiogenic treatment strategies for corneal and ocular surface diseases. (2013)
  • Author(s): Bock F, Maruyama K, Regenfuss B, Hos D, Steven P, Heindl LM, Cursiefen C.
  • Journal Title: Prog Retin Eye Res Volume: 34 Pages: 89-124
  • Peer Reviewed
• [Journal Article] Deletion of Tetraspanin CD9 Diminishes Lymphangiogenesis in Vivo and in Vitro. (2013)
  • Author(s): Iwasaki T, Takeda Y, Maruyama K, Yokosaki Y, Tsujino K, Tetsumoto S, Kuhara H, Nakanishi K, Otani Y, Jin Y, Kohmo S, Hirata H, Takahashi R, Suzuki M, Inoue K, Nagatomo I, Goya S, Kijima T, Kumagai T, Tachibana I, Kawase I, Kumanogoh A.
  • Journal Title: J Biol Chem Volume: 288 Pages: 2118-2131
  • Peer Reviewed
• [Journal Article] Critical role of Nrf2 in oxidative stress-induced retinal ganglion cell death (2013)
  • Author(s): Himori N, Yamamoto K, Maruyama K, Ryu M, Taguchi K, Yamamoto M, Nakazawa T.
  • Journal Title: J Neurochem Volume: 127 Issue: 5 Pages: 669-680
  • DOI: 10.1111/jnc.12325
  • Peer Reviewed
• [Journal Article] Intraocular Invasion of Adult T-Cell Leukemia Cells without Systemic Symptoms after Cataract Surgery. (2013)
  • Author(s): Maruyama K, Nagata K, Kojima K, Inaba T, Sugita S, Mochizuki M, Kinoshita S.
  • Journal Title: Case Report in Ophthalmology Volume: 4 Pages: 252-256
  • Peer Reviewed
• [Journal Article] Deletion of tetraspanin CD9 diminishes lymphangiogenesis in vivo and in vitro. (2013)
  • Author(s): Iwasaki T, Takeda Y, Maruyama K, etc
  • Journal Title: J Biol Chem. Volume: 288 Issue: 4 Pages: 2118-2131
  • DOI: 10.1074/jbc.m112.424291
  • Peer Reviewed
• [Journal Article] Novel anti(lymph)angiogenic treatment strategies for corneal and ocular surface diseases. (2013)
  • Author(s): Bock F, Maruyama K, Regenfuss B, Hos D, Steven P, Heindl LM, Cursiefen C.
  • Journal Title: Prog Retin Eye Res. Volume: in press Pages: 89-124
  • DOI: 10.1016/j.preteyeres.2013.01.001
  • Peer Reviewed
• [Journal Article] Forskolin Modifies Retinal Vascular Development in Mrp4-knockout Mice (2012)
  • Author(s): Matsumiya W, Kusuhara S, Hayashibe K, Maruyama K, Kusuhara H, Tagami M, Schuetz JD, Negi A
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 53(13) Pages: 8029-35
  • Peer Reviewed
• [Journal Article] Topical simvastatin accelerates wound healing in diabetes by enhancing angiogenesis and lymphangiogenesis (2012)
  • Author(s): Asai J, Takenaka H, Hirakawa S, Sakabe J, Hagura A, Kishimoto S, Maruyama K, Kajiya K, Kinoshita S, Tokura Y, Katoh N
  • Journal Title: Am J Pathol Volume: 181(6) Pages: 2217-24
  • Peer Reviewed
• [Journal Article] The CD4/CD8 ratio in vitreous fluid is of high diagnostic value in sarcoidosis (2012)
  • Author(s): Kojima K, Maruyama K, Inaba T, Nagata K, Yasuhara T, Yoneda K, Sugita S, Mochizuki M, Kinoshita S
  • Journal Title: Ophthalmology Volume: 119(11) Pages: 2386-92
  • Peer Reviewed
• [Journal Article] Immunosuppressive properties of regulatory T cells generated by incubation of peripheral blood mononuclear cells with supernatants of human RPE cells (2012)
  • Author(s): Imai A, Sugita S, Kawazoe Y, Horie S, Yamada Y, Keino H, Maruyama K, Mochizuki M
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 53(11) Pages: 7299-309
  • Peer Reviewed
• [Journal Article] Primary intraocular large B cell lymphoma with plasmacytic differentiation (2012)
  • Author(s): Inaba T, Nagata K, Maruyama K
  • Journal Title: Int J Hematol Volume: 96(4) Pages: 399-400
  • NAID: 10031126728
  • Peer Reviewed
• [Journal Article] The maintenance of lymphatic vessel in the cornea is dependent on the presence of macrophage (2012)
  • Author(s): Maruyama K, Nakazawa T, Cursiefen C, Maruyama Y, Rooijen N, D'Amore P, Kinoshita S
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 53(6) Pages: 3145-53
  • Peer Reviewed
• [Journal Article] Simultaneous Analysis of Multiple Cytokines in the Vitreous of Patient with Sarcoid Uveitis (2012)
  • Author(s): Nagata K, Maruyama K, Uno K, Shinomiya K, Yoneda K, Hamuro J, Sugita S, Yoshimura T, Sonoda KH, Mochizuki M, Kinoshita S
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 53(7) Pages: 3827-33
  • Peer Reviewed
• [Journal Article] Heat treatment of retinal pigment epithelium induces production of elastic lamina components and antiangiogenic activity (2012)
  • Author(s): Sekiyama E, Saint-Geniez M, Yoneda K, Hisatomi T, Nakao S, Walshe TE, Maruyama K, Hafezi-Moghadam A, Miller JW, Kinoshita S, D'Amore PA
  • Journal Title: FASEB J Volume: 26(2) Pages: 567-75
  • Peer Reviewed
• [Journal Article] The maintenance of lymphatic vessels in the cornea is dependent on the presence of macrophages (2012)
  • Author(s): Maruyama K, Nakazawa T, Cursiefen C, Maruyama Y, Van Rooijen N, D'Amore PA, Kinoshita S.
  • Journal Title: Invest Ophthalmol Vis Sci. Volume: 53 Issue: 6 Pages: 3145-3153
  • DOI: 10.1167/iovs.11-8010
  • Peer Reviewed
• [Journal Article] Topical simvastatin accelerates wound healing in diabetes by enhancing angiogenesis and lymphangiogenesis (2012)
  • Author(s): Jun Asai
  • Journal Title: The American Journal of Pathology Volume: 181 Issue: 6 Pages: 2217-2224
  • DOI: 10.1016/j.ajpath.2012.08.023
  • Peer Reviewed
• [Journal Article] The maintenance of lymphatic vessel in the cornea is dependent on the presence of macrophage (2012)
  • Author(s): Maruyama K, Nakazawa T, Cursiefen C, Maruyama Y, Rooijen N, D'Amore P, Kinoshita S
  • Journal Title: Invest Ophthalmol Vis Sci. Volume: In press
  • Peer Reviewed
• [Journal Article] Interferon treatment possibly induced endogenous mycotic endophthalmitis (2011)
  • Author(s): Cho Y, Maruyama K, Sugita S, Mochizuki M, Kinoshita S
  • Journal Title: J Clinic Experimental Ophthalmol Volume: 2 Pages: 193-193
  • Peer Reviewed
• [Journal Article] Thrombospondin 1 inhibits inflammatory lymphangiogenesis by CD36 ligation on monocytes (2011)
  • Author(s): Cursiefen C, Maruyama K, Bock F, Saban D, Sadrai Z, Lawler J, Dana R, Masli S
  • Journal Title: J Exp Med Volume: 208(5) Pages: 1083-92
  • Peer Reviewed
• [Journal Article] Suppression of phagocytic cells in retinal disorders using amphiphilic poly(γ-glutamic acid) nanoparticles containing dexamethasone (2011)
  • Author(s): Ryu M, Nakazawa T, Akagi T, Tanaka T, Watanabe R, Yasuda M, Himori N, Maruyama K, Yamashita T, Abe T, Akashi M, Nishida K
  • Journal Title: J Control Release Volume: 151(1) Pages: 65-73
  • Peer Reviewed
• [Presentation] Corneal Endothelial Cell Density and Filtration Surgery in Patients with Posner-Schlossman Syndrome (2013)
  • Author(s): Maruyama K, Maruyama Y, Kato Y, Maruyama Y, Mori K, Ueno M, Ikeda Y, Kinoshita S
  • Organizer: ARVO
  • Place of Presentation: Seattle, USA
• [Presentation] Useful Diagnostic Tool for Progressive Visual Acuity Decrease in Glaucoma Patients (2013)
  • Author(s): Yabana T, Omodaka K, Takahashi M, Himori N, Ryu M, Maruyama K, Nakazawa T
  • Organizer: ARVO
  • Place of Presentation: Seattle, USA
• [Presentation] The Comparison of Podoplanin Expression Between Choroidal and Conjunctival Melanoma (2013)
  • Author(s): Maruyama K, Usui Y, Ueda S, Maruyama Y, Goto H, Nakazawa T
  • Organizer: ARVO
  • Place of Presentation: Seattle, USA
• [Presentation] Vogt-小柳-原田病と類似したAPMPPEの2例 (2013)
  • Author(s): 橋本清香、丸山和一、國方彦志、阿部俊明、中澤徹
  • Organizer: 第67回日本臨床眼科学会
  • Place of Presentation: 東京 (一般講演)
• [Presentation] 眼サルコイドーシスと裂孔原性網膜剥離における網膜生検組織の比較 (2013)
  • Author(s): 永田健児、丸山和一、米田一仁、畑中宏樹、江石義信、木下茂
  • Organizer: 第67回日本臨床眼科学会
  • Place of Presentation: 東京 (一般講演)
• [Presentation] 線維柱帯切除後の濾過胞における経時的結膜血管面積の定量化 (2013)
  • Author(s): 浅野俊文、津田聡、國分太貴、横山悠、面高宗子、渡邉亮、劉孟林、国松志保、高橋秀肇、丸山和一、中澤徹
  • Organizer: 第67回日本臨床眼科学会
  • Place of Presentation: 東京 (学術展示)
• [Presentation] 眼内炎症性疾患の硝子体細胞解析について (2013)
  • Author(s): 丸山和一、稲葉亨、清水愛、國方彦志、木下茂、中澤徹
  • Organizer: 第67回日本臨床眼科学会
  • Place of Presentation: 東京 (一般講演)
• [Presentation] ラット視神経切断後早期の電気生理学・分子生物学的検討 (2013)
  • Author(s): 雪田昌克、面高宗子、丸山和一、町田繁樹、中澤徹
  • Organizer: 第24回日本緑内障学会
  • Place of Presentation: 東京 (ポスター発表)
• [Presentation] 東北大学病院における毛様体光凝固術の術後成績 (2013)
  • Author(s): 多田麻子、国松志保、丸山和一、高橋秀肇、劉孟林、渡邉亮、檜森紀子、横山悠、津田聡、志賀由己浩、中澤徹
  • Organizer: 第24回日本緑内障学会
  • Place of Presentation: 東京 (ポスター発表)
• [Presentation] 視神経挫滅モデルにおけるROCK阻害薬K-115の神経保護効果 (2013)
  • Author(s): 山本耕太郎、丸山和一、檜森紀子、中澤徹
  • Organizer: 第24回日本緑内障学会
  • Place of Presentation: 東京
• [Presentation] Correlation of cytokines in the aqueous humor and functional prognosis of the bleb after trabeculectomy(濾過胞の生存に関与する前房水サイトカインの検討) (2013)
  • Author(s): 國分太貴、津田聡、安田正幸、清水愛、横山悠、渡邉亮、劉孟林、国松志保、丸山和一、中澤徹
  • Organizer: 第24回日本緑内障学会
  • Place of Presentation: 東京 (English Session)
• [Presentation] 難治性ポスナーシュロスマン症候群における観血的治療症例の特徴 (2013)
  • Author(s): 丸山和一、丸山悠子、森和彦、劉孟林、国松志保、木下茂、中澤徹
  • Organizer: 第24回日本緑内障学会
  • Place of Presentation: 東京
• [Presentation] ウィルス性ぶどう膜炎における硝子体細胞解析について (2013)
  • Author(s): 丸山和一、稲葉亨、國方彦志、望月學、木下茂、中澤徹
  • Organizer: 第47回日本眼炎症学会
  • Place of Presentation: 大阪
• [Presentation] マウス視神経挫滅モデルにおけるNrf2活性剤の神経保護効果 (2013)
  • Author(s): 檜森紀子、丸山和一、山本耕太郎、田口恵子、劉孟林、山本雅之、中澤徹
  • Organizer: 第13回抗加齢医学学会
  • Place of Presentation: 横浜
• [Presentation] エリスロポエチンノックアウトマウスを用いた網膜・視神経の組織学的検討 (2013)
  • Author(s): 安田正幸、劉孟林、田中佑治、檜森紀子、面高宗子、横山悠、雪田昌克、津田聡、丸山和一、山本雅之、中澤徹
  • Organizer: 第117回日本眼科学会総会
  • Place of Presentation: 東京
• [Presentation] he Comparison of Podoplanin Expression Between Choroidal and Conjunctival Melanoma (2013)
  • Author(s): Maruyama K, Usui Y, Ueda S, Maruyama Y, Goto H, Nakazawa T.
  • Organizer: The Association for Research in Vision and Ophthalmology (ARVO) 2013, Annual meeting,
  • Place of Presentation: Seattle, U.S.A
• [Presentation] The Comparison of T-Cell Population in Uveitis Vitreous Fluid. (2013)
  • Author(s): Maruyama K.
  • Organizer: American Academy of Ophthalmology（AAO）2013, Annual meeting
  • Place of Presentation: New Orleans, USA,
• [Presentation] The CD4/CD8 ratio in vitreous fluid (VLF) is of high diagnostic value as same as bronchoalveolar lavage fluid (BALF) in sarcoidosis. (2013)
  • Author(s): Maruyama K
  • Organizer: International Ophthalmology Symposium at Seoul National University Hospital
  • Place of Presentation: Seoul, Korea
  • Invited
• [Presentation] ウィルス性ぶどう膜炎における硝子体細胞解析について (2013)
  • Author(s): 丸山和一、稲葉亨、國方彦志、望月學、木下茂、中澤徹
  • Organizer: 第47回日本眼炎症学会
  • Place of Presentation: 大阪市
• [Presentation] 眼内炎症性疾患の硝子体細胞解析について (2013)
  • Author(s): 丸山和一、稲葉亨、清水愛、國方彦志、木下茂、中澤徹
  • Organizer: 第67回 日本臨床眼科学会
  • Place of Presentation: 横浜
• [Presentation] Cytokine Levels In The Vitreous Fluid Of Patients With Ocular Sarcoidosis And Patients With Diabetic Retinopathy (2012)
  • Author(s): Nagata K, Maruyama K, Yoneda K, Yoshimura T, Sonoda K-H, Kinoshita S
  • Organizer: ARVO
  • Place of Presentation: Ft. Lauderdale, U.S.A
• [Presentation] Suppression Of Corneal Lymphangiogenesis And Rejection Reaction After Corneal Transplantation By Using An Anti-podoplanin Antibody (2012)
  • Author(s): Maruyama Y, Maruyama K, Kato Y, Kinoshita S
  • Organizer: ARVO
  • Place of Presentation: Ft. Lauderdale, U.S.A
• [Presentation] Suppression of Corenal Lymphangiogenesis and Rejection Reaction after Corneal Transplantation by Using an Anti-podoplanin antibody (2012)
  • Author(s): Maruyama K, Maruyama Y, Kato Y, Kerjaschki D, Kinoshita S
  • Organizer: Molecular Mechanisms in Lymphatic Function and Disease
  • Place of Presentation: Ventura CA (Gordon research conference)
• [Presentation] Suppression of lymphangiogenesis and rejection reaction after corneal transplantation by using an anti-podoplanin antibody (PMab-1) (2012)
  • Author(s): Maruyama K, Maruyama Y, Kato Y, Kinoshita S
  • Organizer: ARVO
  • Place of Presentation: Ft. Lauderdale, U.S.A
• [Presentation] Podoplanin制御による角膜リンパ管新生と角膜移植後拒絶反応の抑制 (2012)
  • Author(s): 丸山悠子、丸山和一、加藤幸成、木下茂
  • Organizer: 第１１６回日本眼科学会総会
  • Place of Presentation: 東京
• [Presentation] Supression of Corneal Lymphangiogenesis and Rejection Reaction after Corneal Transplantation by Using and Anti-Podoplanin antibody (2012)
  • Author(s): Maruyama K, Maruyama Y, Kato Y, Kerjaschki D, Kinoshita S
  • Organizer: Gordon Research Conference, Molecular Mechanism in Lymphatic Function and Disease
  • Place of Presentation: Ventura CA, USA
• [Book] ぶどう膜炎を斬る．専門医のための眼科診療クオリファイ 内因性ぶどう膜炎 Posner-Schlossman症候群 (2013)
  • Author(s): 丸山和一
  • Publisher: 中山書店