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2005 Fiscal Year Final Research Report Summary

Analysis of glaucoma-related protein interaction

Research Project

Project/Area Number 16591779
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Ophthalmology
Research InstitutionNational Hospital Organization Tokyo Medical Center

Principal Investigator

IWATA Takeshi  National Hospital Organization Tokyo Medical Center, National Institute of Sensory Organs, Laboratory Head, 視覚研究部門, 室長 (90374157)

Co-Investigator(Kenkyū-buntansha) NISHIMURA Toshihide  Tokyo Medical College, Clinical Proteome Research Center, Professor, 臨床プロテオーム研究センター, 教授 (40366092)
Project Period (FY) 2004 – 2005
Keywordsglaucoma / optineurin / Rab8 / retinal ganglion cells / protein interaction / quartz crystal balance / gene mutation / intra ocular pressure
Research Abstract

Glaucoma is one of the leading causes of blindness affecting 70 million people world wide. Glaucoma is often associated with elevated intraocular pressure (IOP) which leads to specific cell death of the retinal ganglion cells (RGC). However, patients with normal tension glaucoma (NTG), a subtype of primary open angle glaucoma (POAG), are affected without the elevation of IOP. In Japan, more than 98% of patients affected by POAG are diagnosed as NTG. Molecular pathways leading to the pathology of the disease are still unclear mainly due to the lack of information of proteins responsible for the disease.
We have focused on optineurin (OPTN), which was identified as the first gene for NTG. Do to the location of the mutation E50K, which is responsible for severe NTG, we decided to analyze the protein-protein interaction between OPTN and Rab8. Interaction was measured by Quartz-Crystal Microbalance (QCM) and GST-pull down assay. All OPTN mutants and Rab8 where expressed in bacteria and purified by affinity chromatography and gel filtration. Each mutant was added to the reaction chamber where wild type Rab8 was fixed on QCM sensor chip. Only E50K showed no interaction with Rab8. This result was later confirmed by the pull down assay.
Rab8 belongs to the family of Rab8 GTP-binding proteins which is functionally known to regulate protein trafficking in the cell. Disruption of interaction between OPTN-Rab8 may explain the cause of specific cell death of retinal ganglion cells (RGC). We are currently over expressing the mutant E50K to observe organelle change in RGC.

  • Research Products

    (13 results)

All 2006 2005 2004

All Journal Article (11 results) Book (2 results)

  • [Journal Article] Complement Factor H Polymorphisms in Japanese Population with Age-Related Macular Degeneration.2006

    • Author(s)
      Okamoto et al.
    • Journal Title

      Mol Vis 12

      Pages: 156-158

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Involvement of Insulin-like Growth Factor-I and Insulin-like Growth Factor Binding Protein-3 in Corneal Fibroblasts during Corneal Wound Healing.2006

    • Author(s)
      Izumi et al.
    • Journal Title

      Invest Ophthal Vis Sci 47

      Pages: 591-598

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Molecular composition of drusen and possible involvement of anti-retinal autoimmunity in two different forms of macular degeneration in cynomolgus monkey (Macaca fascicularis).2005

    • Author(s)
      Umeda et al.
    • Journal Title

      FASEB J 19

      Pages: 1683-1685

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Early onset macular degeneration with drusen in a cynomolgus monkey (Macaca fascicularis) pedigree caused by a novel gene mutation.2005

    • Author(s)
      Umeda et al.
    • Journal Title

      Invest Ophthal Vis Sci 46

      Pages: 683-691

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 「研究成果報告書概要(欧文)」より2005

    • Author(s)
      Umeda S, et al.
    • Journal Title

      FASEB 19

      Pages: 1683-1685

  • [Journal Article] 「研究成果報告書概要(欧文)」より2005

    • Author(s)
      Umeda S, et al.
    • Journal Title

      Invest Ophthal Vis Sci 46

      Pages: 683-691

  • [Journal Article] 「研究成果報告書概要(欧文)」より2004

    • Author(s)
      Funayama T, et al.
    • Journal Title

      Invest Ophthal Vis Sci 45

      Pages: 4359-4367

  • [Journal Article] 「研究成果報告書概要(欧文)」より2004

    • Author(s)
      Ishikawa K, et al.
    • Journal Title

      J Glaucoma 13

      Pages: 466-471

  • [Journal Article] 「研究成果報告書概要(欧文)」より2004

    • Author(s)
      Niizeki H, et al.
    • Journal Title

      J Dermatol Sci 35

      Pages: 221-223

  • [Journal Article] 「研究成果報告書概要(欧文)」より2004

    • Author(s)
      Obazawa M, et al.
    • Journal Title

      Invest Ophthal Vis Sci 45

      Pages: 2652-2659

  • [Journal Article] 「研究成果報告書概要(欧文)」より2004

    • Author(s)
      Tanaka Y, et al.
    • Journal Title

      Invest Ophthal Vis Sci 45

      Pages: 245-252

  • [Book] 打倒!加齢黄斑変性2006

    • Author(s)
      岩田 岳
    • Total Pages
      170
    • Publisher
      メディカル・ビュー
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] Handbook of Models for Human Aging2006

    • Author(s)
      Hejtmancik et al.
    • Total Pages
      850
    • Publisher
      Academic Press, Elsevier Inc.
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2008-05-27  

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