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The role of leukocyte in the pathogeuesis of diabctic retiuoparthy

Research Project

Project/Area Number 11671733
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Ophthalmology
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

KIRYU Junichi  Kyoto University, Dept. of Ophthalmology, Lecturer, 医学研究科, 講師 (80281096)

Co-Investigator(Kenkyū-buntansha) TAKAGI Hitoshi  Kyoto University, Dept. of Ophthalmology, Lecturer, 医学研究科, 講師 (70283596)
KASHII Satoshi  Kyoto University, Dept. of Ophthalmology, Assoc. Professor, 医学研究科, 助教授 (50194717)
HONDA Yoshihito  Kyoto University, Dept. of Ophthalmology, Professor, 医学研究科, 教授 (90026930)
MANDAI Michiko  Kyoto University, Dept. of Ophthalmology, Instructor, 医学研究科, 助手 (80263086)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1999: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordsleukocyte / retina / diabetes
Research Abstract

Recently, leukocytes are thought to play a central role in inflammatory conditions such as ischemia-reperfusion injury and endotoxin-induced uveitis. At inflammatory sites, the recruitment of circulating leukocytes out of the vessels is thought to occur through a multistep cascade of leukocyte-endothelial interactions, involving sequential rolling, firm adhesion, and transmigration into inflamed tissues. During this multistep cascade of leukocyte infiltration, each process is mediated with distinct adhesion molecules and regulated elaborately.
Diabetes is associated with greater neural damage after transient cerebral ischemia. Using rats with streptozotocin-induced diabetes of 4 weeks duration, we investigated leukocyte-endothelial cell interactions after ischemia-reperfusion injury. Leukocyte rolling and accumulation throughout the period of reperfusion was significantly suppressed in diabetic rats compared with non-diabetic rats. In addition, neither preischemic insulin treatment to d … More iabetic rats nor preischemic glucose infusion to non-diabetic rats had a significant influence on leukocyte-endothelial cells interactions during reperfusion. High blood glucose concentration before induction of ischemia did not exacerbate leukocyte involvement in the postischemic retinal injury. In conclusion, diabetic retina showed suppressed leukocyte-endothelial cells interactions after transient ischemia, perhaps due to an adaptive mechanism that developed during the period of induced diabetes.
EIU is characterized by blood ocular barrier disruption and leukocyte infiltration. The treatment with ATIII, leukocyte rolling was substantially inhibited along the retinal veins, suppressing subsequent leukocyte infiltration into the vitreous cavity. Similarly, leukocyte infiltration and protein leakage into the aqueous humor were significantly reduced with ATlll treatment. The levels of P-selectin mRNA expression in both iris-ciliary body and retina, which were upregulated after LPS injection, were substantially lower in the ATIII-treated rats. ATIII treatment significantly inhibited inflammatory reactions induced with LPS.Its suppressive effects on P-selectin expression could contribute to the attenuation of leukocyte infiltration, possibly by inhibiting leukocyte rolling. The current findings suggest the therapeutic potency of ATIII for the treatment of inveterate veitis. Less

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] A.Tsujikawa: "Leukocyte-endothelial cell interactions in diabetic retina after transient retinal ischemia."Am J Physiol Regulatory Integrative comp Physiol. 279(3). 980-989 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] A.Tsujikawa: "Interactions between blood cells and retinal endothelium in endotoxic sepsis"Hypertension. 36(2). 250-258 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] A.Nonaka: "PKC-β inhibitor (LY333531) attenuates leukocyte entrapment in retinal microcirculation of diabetic rats."Invest Ophthalmol Vis Sci. 41(9). 2702-2706 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] A.Nonaka: "Administration of 17β-estradiol attenuates retinal ischemia-reperfusion injury in rats."Invest Ophthalmol Vis Sci. 41(9). 2689-2696 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] A.Tsujikawa: "In vivo evaluation of platelet-endothelial interactions in retinal microcirculation of rats."Invest Ophthalmol Vis Sci. 40(12). 2918-2924 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] N.Hiroshiba: "Radiation-induced leukocyte entrapment in the rat retinal microcirculation."Invest Ophthalmol Vis Sci. 40(6). 1217-1222 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tsujikawa-A ; Kiryu-J ; Dong-J, et al.: "Quantitative analysis of diabetic macular edema after scatter laser photocoagulation with the scanning retinal thickness analyzer."Retina.. 19(1). 59-64 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tsujikawa-A ; Ogura-Y ; Hiroshiba-N, et al.: "Retinal ischemia-reperfusion injury attenuated by blocking of adhesion molecules of vascular endothelium."Invest-Ophthalmol-Vis-Sci.. 40(6). 1183-90 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tsujikawa-A ; Kiryu-J ; Nonaka-A, et al.: "In vivo evaluation of platelet-endothelial interactions in retinal microcirculation of rats."Invest-Ophthalmol-Vis-Sci.. 40(12). 2918-24 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Miyamoto-K, Ogura Y.: "Pathogenetic potential of leukocytes in diabetic retinopathy."Seminars in Ophthalmol.. 14. 233-239 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nonaka-A ; Kiryu-J ; Tsujikawa-A, et al.: "Administration of 17beta-estradiol attenuates retinal ischemia-reperfusion injury in rats."Invest-Ophthalmol-Vis-Sci.. 41(9). 2689-96 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nonaka-A ; Kiryu-J ; Tsujikawa-A, et al.: "PKC-beta inhibitor (LY333531) attenuates leukocyte entrapment in retinal microcirculation of diabetic rats."Invest-Ophthalmol-Vis-Sci.. 41(9). 2702-6 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tsujikawa-A ; Kiryu-J ; Yamashiro-K, et al.: "Interactions between blood cells and retinal endothelium in endotoxic sepsis."Hypertension.. 36(2). 250-8 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tsujikawa-A ; Kiryu-J ; Nonaka-A, et al.: "Leukocyte-endothelial cell interactions in diabetic retina after transient retinal ischemia."Am-J-Physiol-Regul-Integr-Comp-Physiol. Sep.. 279(3). R980-9 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] A.Tsujikawa: "Leukocyte-endothelial cell interactions in diabetic retina after transient retinal ischemia."Am J Physiol Regulatory Integrative Corp Physiol. 279(3). 980-989 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] A.Tsujikawa: "Interactions between blood cells and retinal endothelium in endotoxic sepsis"Hypertension. 36(2). 250-258 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] A.Nonaka: "PKC-β inhibitor (LY333531) attenuates leukocyte entrapment in retinal microcirculation of diabetic rats."Invest Ophthalmol Vis Sci. 41(9). 2702-2706 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] A.Nonaka: "Administration of 17β-estradiol attenuates retinal ischemia-reperfusion injury in rats."Invest Ophthalmol Vis Sci. 41(9). 2689-2696 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] A.Tsujikawa: "In vivo evaluation of platelet-endothelial interactions in retinal microcirculation of rats"Invest Ophthalmol Vis Sci. 40(12). 2918-2924 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] N.Hiroshiba: "Radiation-induced leukocyte eutrapment in the rat retinal microcirculation."Invest Ophthalmol Vis Sci. 40(6). 1217-1222 (1999)

    • Related Report
      2000 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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