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Study on the mechanisms of leukocyte-endothelial interactions in retinal microcirculation

Research Project

Project/Area Number 10470364
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Ophthalmology
Research InstitutionNAGOYA CITY UNIVERSITY

Principal Investigator

OGURA Yuichiro  NAGOYA CITY UNIVERSITY, MEDICAL SCHOOL, PROFESSOR, 医学部, 教授 (70191963)

Co-Investigator(Kenkyū-buntansha) TOMIDA Kazuyuki  NAGOYA CITY UNIVERSITY, MEDICAL SCHOOL, Research Associate, 医学部, 助手 (40305537)
OZEKI Hironori  NAGOYA CITY UNIVERSITY, MEDICAL SCHOOL, ASSISTANT PROFESSOR, 医学部, 講師 (60254299)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥13,200,000 (Direct Cost: ¥13,200,000)
Fiscal Year 2000: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 1999: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 1998: ¥4,700,000 (Direct Cost: ¥4,700,000)
Keywordsleukocyte / retinal circulation / choroidal circulation / retinal ischemia reperfusion injury / diabetic retinopathy / 接着分子 / 血管内皮 / acridine orange / 網膜虚血再灌流
Research Abstract

Acridine orange leukocyte fluography was applied to study leukocyte dynamics in the following experimentally induced microcirculatory disturbance of the retina : ischemia-reperfusion injury of the retina and experimental diabetes mellitus.
1. Ischemia-reperfusion injury of the retina
During reperfusion period after transient (60 min) retinal ischemia by optic nerve ligation, the rolling of leukocytes in the retinal veins was prominent and numerous leukocytes were trapped in the retinal capillaries. The numbers of rolling leukocytes were at maximum 12 hours after reperfusion. Leukocyte entrapment was peaked at 24 hours after reperfusion. By blocking adhesion molecules on the vascular endothelium, these leukocyte-endothelial interactions were effectively inhibited. Postischemic retinal atrophy was also inhibited by blocking adhesion molecules. These results suggested that leukocytes may be major players in the pathophysiology of ischernia reperfusion injury of the retina.
2 Experimental diabetes mellitus
Leukocyte dynamics in the retina were studied in streptozotocin-induced disbetes and spontaneous diabetes (OLEIF rat). In the both diabetic models, leukocytc entrapment in the retinal capillaries was increased even in the early stages of diabetes. Fluorescein angiography revealed that trapped leukocyte disturbed the regional capillary blood flow in the downstream. Enhanced expression of adhesion molecules was observed in the capillary endothelium of the retina in the diabetic rats. Leukocyte entrapment in the retinal capillaries might cause microvascular occlusions and dysfunction, in tum causing diabetic retinopathy.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Tsujikawa A, et al.: "Retinal ischemia-reperfusion injury attenuated by blocking of adhesion molecules of vascular endothelium."Invest Ophthalmol Vis Sci. 40. 1183-1190 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hiroshiba N, et al.: "Radiation-induced leukocyte entrapment in rat retinal microcirculation."Invest Ophthalmol Vis Sci. 40. 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] Matsubara A, et al.: "Protective effects of selectin ligands/inhibitor (SKK-60060) against retinal ischemia-reperfusion injury."Exp Eye Res. 71. 283-293 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tsujikawa A, Ogura Y, Hiroshiba N, Miyamoto K, Kiryu J, Tojo S, Miyasaka M, Honda Y: "Retinal ischemia-reperfusion injury attenuated by blocking of adhesion molecules of vascular endothelium"Invest Ophthabnol Vis Sci. 40. 1183-1190 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hiroshiba N, Ogura Y, Sasai K, Nishiwaki H, Miyamoto K, Hamada M, Tsujikawa A, Honda Y: "Radiation-induced leukocyte entrapment in rat retinal microcirculation"Invest Ophthalmol Vis Sci. 40. 1217-1222 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Matsubara A, Tomida K, Matsuda Y, Tamai K, Tashita A, Jomori T, Tsujikawa A, Ogura Y: "Protective effects of selectin ligands/mhibitor (SKK-60060) against retinal ischemia-reperfusion injury"Exp Eye Res. 71. 283-293 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Matsubara A, et al: "Protective effects of selectin ligands/inhibitor (SKK-60060) against retinal ischemia-reperfusion injury."Exp Eye Res. 71. 283-293 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tsujikawa A, et al: "Retinal ischemia-reperfusion injury attenuated by blocking of adhesion molecules of vascular endothelium"Invest Ophtalmol Vis Sci. 40. 1183-1190 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hiroshiba N, et al: "Rediation-induced leukocyte entrapment in rat retinal microcirculation"Invest Ophthalmol Vis Sci. 40. 1217-1222 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Miyamoto K, et al: "Prevention of leukostasis and vascular leakage in streptozotocin-induced diabetic retinopathy via intercellular adhesion molecule-1 inhibition"Proc Natl Sci USA. 96. 10836-10841 (1999)

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

    • Related Report
      1999 Annual Research Report
  • [Publications] Tsujikawa,A.et al: "In Vivo evalution of toukeryte dynamics in retinal is hemia reperfusion injury" Invest Ophthalmol Vis Sci. 39. 793-800 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hiroshiba N et al: "Alterations of retinal mlcroclrculation in response to scatter phetocongulation" Invest Ophthalmol Vis Sci. 39. 767-776 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tsujikawa A.et al: "Tacrolimus (FK506)α tfenuates lfukocyte accumulation after tmnsient retinal ischemia" Stroke. 29. 1431-1438 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Miyamoto K.et al: "In vivo demonstration of increased leukocyte entrapment in retinal microcirculation of diabetic rats" Imest Ophthalmol Vis Sci. 39. 2190-2194 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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