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Study of autoimmune mechanisms in molecular pathology of glaucomatous optic neuropathy.

Research Project

Project/Area Number 14571653
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Ophthalmology
Research InstitutionHirosaki University

Principal Investigator

OHGURO Ikuyo  Hirosaki University, School of Medicine, Ophthalmology, assistant professor, 医学部, 講師 (90305235)

Co-Investigator(Kenkyū-buntansha) OHGURO Hiroshi  Hirosaki University, School of Medicine, associate professor, 医学部, 助教授 (30203748)
NAKAZAWA Mitsuru  Hirosaki University, School of Medicine, professor, 医学部, 教授 (80180272)
間宮 和久  弘前大学, 医学部附属病院, 助手 (60344610)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywordsglaucoma / optic nerve / autoimmunity / retinal ganglion cell / autoantibody / apoptosis / neuron specific enolase(NSE) / calcium antagonist / 神経保護 / ニューロン特異エノラーゼ
Research Abstract

Purpose : To evaluate further the clinical roles of serum autoantibody against neuron specific enolase(NSE) in glaucoma patients and its pathilogical effects on retina. Subjects and methods : Serum autoantibody against NSE was examined by western blot analysis and enzyme-linke immunosorbent assay in 73 patients with normal tension galucoma(NTG) and 169 patients with primary open angle glaucoma(POAG), and the relationships between the titers of anti-NSE antibody and clinical characteristics were evaluated. Either a glaucoma patient's serum or purified anti-NSE antibody was intravrtreously administrated into Lewis rat eyes, and electrophysiological, histopathological, and biochemical evaluations were performed. In addition, the neuroprotective effects of anti-glaucoma drugs and a calcium antagonist were studied using these animal models. Results : Anti-NSE antibody was recognized in about 20% of glaucoma patients. The titers of anti-NSE antibody showed a regular decreasing pattern with d … More eteriorating visual field losses in POAG, but no systematic pattern was observed in NTG. The anti-NSE antibody titers were relatively higher in NTG with visual field deterioration than in those without it. Electron microsdopy revealed that intravitreal administration of a glaucoma patient's serum, which immunoreacted with retinal 50kDa in western blot analysis, and purified anti-NSE antibody induced retinal ganglion cell apoptosis in rat eyes. Functionally, these eyes showed a significant decrease in ERG responses and a remarkable decrease in rhodopsin phosphorylation reaction. Co-administration of nipradilol or betaxolol with anti-NSE antibody caused marked recovery of the affected ERG responses or a recovery effect on decreased rhodopsin phosphorylation, respectively. Nilvadipine functioned beneficially on both impaired ERG and rhodopsin phospharylation reactions. Cnnclusions : These observations suggest that serum autoantibody against NSE may be clinically useful for diagnosing early stages of POAG, and for monitoring glaucoma progression of NTG and that serum autoantibody against NSE found in some patients with glaucoma induces retinal dysfunction in vivo. Less

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] Maruyama I, et al.: "Autoantibody against neuron-specific enolase found in glaucoma patients cause retinal dysfunction in vivo."Jpn J Ophthalmol. 46. 1-12 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Maruyama I, et al.: "Clinical roles of serum autoantibody against Neuron-specific enolase in glaucoma patients."Tohoku J Exp Med. 197. 125-132 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ikeda Y, Maruyama I et al.: "Clinical significance of serum antibody against neuron-specific enolase in glaucoma patients."Jpn J Ophthalmol. 46. 13-17 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 丸山幾代, 他: "眼科医のための先端医療緑内障と自己抗体"あたらしい眼科. 19. 329-330 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Marutama I, et al.: "A case of acute angle-closure glaucoma secondary to posterior scleritis in patient with Sturge-Weber syndrome."Jpn J Ophthalmol. 46. 74-77 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ohguro H, Maruyama I, et al.: "A high dietary intake of sodium glutamate as flavoring (Ajinomoto) causes gross changes in retinal morphology and function."Exp Eye Res. 75. 307-315 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 大黒幾代, 他: "先端医療シリーズ23 眼科の最新医療 第5章 緑内障様視神経障害の病態「3.自己免疫」"先端医療技術研究所. 165-167 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Maruyama I, et al.: "Autoantibody against neuron-specific enolase found in glaucoma patients cause retinal dysfunction in vivo."Jpn J Ophthalmol. 46. 1-12 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Maruyama I, Ikeda Y, Nakazawa M, Ohguro H: "Clinical roles of serum autoantibody against Neuron-specific enolase in glaucoma patients."Tohoku J Exp Med. 197. 125-132 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ikeda Y, Maruyama I, Nakazawa M, Ohguro H: "Clinical significance of serum antibody against neuron-specific enolase in glaucoma patients."Jpn J Ophthalmol. 46. 13-17 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Maruyama I, Ohguro H, Nakazawa M: "A case of acute angle-closure glaucoma secondary to posterior scleritis in patient with Sturge-Weber syndrome."Jpn J Ophthalmol. 46. 74-77 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ohguro H, Katsushima H, Maruyama I, et al.: "A high dietary intake of sodium glutamate as flavoring(Ajinomoto) causes gross changes in retinal morphology and function."Exp Eye Res. 75. 307-315 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Maruyama I, Ohguro H: "The glaucoma and aoutoantibodies."Journal of the eye. 19. 329-330 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ohguro I, Ouguro H: "Chapter 5 The patho-physiology of glaucoma-like optic neuropathy. Section3. The autoimmune mechanisms in glaucoma."The modern medical technology in ophthalmology. 165-167 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ohguro H, Ohguro I, Mamiya K, Maeda T, Nakazawa M: "Prolonged survival of the phosphorylated form of rhodopsin during dark adaptation of Royal College Surgeons rat"FEBS Lett.. 551. 128-132 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sato M, Ohguro H, Ohguro I, et al.: "Study of pharmacological effects of nilvadipine on RCS rat retinal degeneration by microarray analysis"Biochem Biophys Res commun. 306. 826-831 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Miyagawa Y, Ohguro H, Odagiri H, Maruyama I, et al.: "Aberrantly expressed recoverin is functionally associated with G-protein-coupled receptor kinases in cancer cell lines"Biochem Biophys Res Commun. 300. 669-673 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ohguro H, Maruyama I, Nakazawa M, Oohira A: "Presence of anti-recoverin antibody within aqueous humor in patient with cancer-associated retinopathy"Am J Ophthalmol. 134. 605-607 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Takano Y, Ohguro H, Ohguro I, et al.: "Low expression of rhodopsin kinase in pineal gland in Royal College Surgeons rat"Cur Eye Res. 27. 95-102 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ohguro H, Tamura M, Kamata Y, Ohguro I, Nakazawa M: "A case of conjunctival malignant melanoma effectively treated by tumor resection and cryotherapy in a 14-year-old boy"Hirosaki Med.J.. 55. 23-28 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Maruyama I.: "Autoantibody against neuron-specific enolase found in glaucoma patients cause retinal dysfunction in vivo"Jpn J Ophthalmol. 46. 1-12 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ikeda Y.: "Clinical significance of serum antibody against neuron-specific enolase in glaucoma patients"Jpn J Ophthalmol. 46. 13-17 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ohguro H.: "A high dietary intake of sodium glutamate as flavoring(Ajinomoto)causes gross changes in retinal morphology and function"Exp Eye Res. 75. 307-315 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Maruyama I.: "Clinical roles of serum autoantibody against Neuron-specific enolase in glaucoma patients"Tohoku J Exp Med. 197. 41-45 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ohguro H.: "Presence of anti-recoverin antibody within aqueous humor in patient with cancer-associated retinopathy. Am J Ophthalmol"Am J Ophthalmol. 134. 605-607 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Maruyama I.: "A case of acute angle-closure glaucoma secondary to posterior scleritis in patient with Sturge-Weber syndrome"Jpn J Ophthalmol. 46. 74-77 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ohguro H.: "Pathological roles of recoverin in Cancer-associated retinopathy. In Photoreceptor and calcium. Eds: K palczewski, W Baehr, in : photoreceptors and calcium"Landes bioscience. 625 (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2022-01-20  

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