Structural and Functional Evaluation of Blood-Ocular-Barrier

• Project/Area Number: 22591953
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Aichi Medical University
• Principal Investigator: ZAKO Masahiro 愛知医科大学, 医学部, 教授 (80298596)
• Co-Investigator(Kenkyū-buntansha): YONEDA Masahiko 愛知県立看護大学, 看護学部, 教授 (80201086)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2012: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: 血液房水関門 / ぶどう膜炎 / 腫瘍壊死因子 / 抗腫瘍壊死因子抗体 / マトリックスメタ ロプロテアーゼ(MMP) / ベーチェット病 / TNF-α / infliximab / マトリックスメタロプロテアーゼ / 毛様体無色素上皮細胞 / 血液眼関門 / 血液網膜関門 / 網膜色素上皮細胞 / 網膜血管内皮細胞 / MMP / TIMP / 細胞外マトリックス

Research Abstract

Induction of matrix metalloproteinases (MMPs) in non-pigmented ciliary epithelium (HNPCECs) by tumor necrosis factor-alpha (TNF-α) was counteracted by infliximab. Immunostaining showed that the MMPs degraded claudin-1 and occludin, major components of the tight junctions in the blood-aqueous barrier, in HNPCECs and in non-pigmented ciliary epithelial cells of the swine ciliary body.

Research Products

• [Journal Article] Infliximab counteracts tumor necrosis factor-α-enhanced induction of matrix metalloproteinases that degrade claudin and occludin in non-pigmented ciliary epithelium. (2013)
  • Author(s): Yamada H, Yoneda M, Inaguma S, Watanabe D, Banno S, Yoshikawa K, Mizutani K, Iwaki M, Zako M.
  • Journal Title: Biochem Pharmacol Volume: in press Issue: 12 Pages: 1770-1782
  • DOI: 10.1016/j.bcp.2013.04.006
  • Peer Reviewed
• [Journal Article] Comparative analysis of hyaluronan's affinity for antivascular endothelial growth factor agents. (2013)
  • Author(s): Sugita I, Yoneda M, Iwaki M, Zako M.
  • Journal Title: Ophthalmic Res. Volume: 49 Issue: 1 Pages: 43-8
  • DOI: 10.1159/000342975
  • Peer Reviewed
• [Journal Article] Intravitreal Injection of Bevacizumab to Treat a Macular Edema Caused by Leber's Miliary Aneurysm. (2012)
  • Author(s): Takeyama M, Iwaki M, Zako M.
  • Journal Title: Case Rep Ophthalmol. Volume: 3 Issue: 3 Pages: 392-5
  • DOI: 10.1159/000345455
  • Peer Reviewed
• [Journal Article] Trabeculotomy in a Behçet's Disease Patient One Week after Infliximab Administration. (2012)
  • Author(s): Koike A, Handa T, Zako M.
  • Journal Title: Case Rep Ophthalmol. Volume: 3 Issue: 1 Pages: 151-5
  • DOI: 10.1159/000338703
  • Peer Reviewed
• [Journal Article] Choroidal and optic disc metastases from breast cancer and their response to combination pharmacotherapy with tamoxifen, cyclophosphamide hydrate, letrozole, and bevacizumab. (2012)
  • Author(s): Zako M, Takeyama M, Naito E, Mizumoto K, Iwaki M.
  • Journal Title: J Ocul Pharmacol Ther. Volume: 28 Issue: 1 Pages: 89-93
  • DOI: 10.1089/jop.2011.0098
  • Peer Reviewed
• [Journal Article] Efficient penetration into aqueous humor by administration of oral and topical levofloxacin (2011)
  • Author(s): Ishida M, Kataoka T, Niwa K, Iwaki M, Zako M
  • Journal Title: J Ocul Pharmacol Ther Volume: 27 Pages: 247-250
  • Peer Reviewed
• [Journal Article] Cataract Surgery in Behcet's Disease Patients One Week after Infliximab Administration (2011)
  • Author(s): Handa T, Tsunekawa H, Zako M
  • Journal Title: Case Report Ophthalmol Volume: 2 Pages: 176-178
  • Peer Reviewed
• [Journal Article] Long-term remission of ocular and extraocular manifestations in Behcet's disease using infliximab (2011)
  • Author(s): Handa T, Tsunekawa H, Yoneda M, Watanabe D, Mukai T, Yamamura M, Iwaki M, Zako M
  • Journal Title: Clin Exp Rheumatol Volume: 4 Suppl 67
  • Peer Reviewed
• [Journal Article] Effect of infliximab on tumor necrosis factor-alpha-induced alterations in retinal microvascular endothelial epithelial cells. (2010)
  • Author(s): Li H, Zako M., et.al
  • Journal Title: J.Ocul Pharmacol Ther. Volume: VOL.26 Pages: 549-556
  • Peer Reviewed
• [Journal Article] Increase in matrix metalloproteinase-2 level in the chicken retina after laser photocoagulation. (2010)
  • Author(s): Takeyama M, Zako M., et.al
  • Journal Title: Lasers Surg Med. Volume: VOL.42 Pages: 433-441
  • Peer Reviewed
• [Journal Article] Infliximab treatment of severe genital ulcers associated with Behcet disease. (2010)
  • Author(s): Kasugai C, Zako M., et.al
  • Journal Title: J Am Acad Dermatol. Volume: VOL.62 Pages: 162-164
  • Peer Reviewed
• [Journal Article] Infliximab counteracts tumor necrosis factor-α-enhanced induction of matrix metalloproteinases that degrade claudin and occludin in non-pigmented ciliary epithelium.
  • Author(s): Yamada H, Yoneda M, Inaguma S, Watanabe D, Banno S, Yoshikawa K, Mizutani K, Iwaki M, Zako M.
  • Journal Title: Biochem Pharmacol. Volume: (in press)
• [Presentation] Infliximab attenuates tumornecrosis factor-α-induced alterations in non-pigmented ciliary epithelium. (2013)
  • Author(s): Yamada H, Yoneda M, Inaguma S, Watanabe D, Banno S, Yoshikawa K, Mizutani K, Iwaki M, Zako M.
  • Organizer: ARVO
  • Place of Presentation: Seattle
  • Year and Date: 2013-05-05
• [Presentation] 光凝固後網膜におけるMMP-2、MMP-9、TIMP-2の経時的変化 (2011)
  • Author(s): 武山正行
  • Organizer: 第115回日本眼科学会総会
  • Place of Presentation: 東京国際フォーラム(東京都)
  • Year and Date: 2011-05-13
• [Presentation] ベーチェット病によるぶどう膜炎と眼外症状に対するinfliximabの長期治療成績 (2011)
  • Author(s): 半田恒明
  • Organizer: 第115回日本眼科学会総会
  • Place of Presentation: 東京国際フォーラム(東京都)
  • Year and Date: 2011-05-13