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Molecular mechanisms of cataract and glaucoma induced by mutations in the Na-HCO3 cotransporter

Research Project

Project/Area Number 13671826
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Ophthalmology
Research InstitutionTokyo Women's Medical University

Principal Investigator

TANAKA Yoshikazu  Tokyo Women's Medical University, 医学部, 助手 (20292922)

Co-Investigator(Kenkyū-buntansha) SHIMIZU Erika  Tokyo Women's Medical University, School of Medicine, Assistant, 医学部, 助手 (50242144)
AMANO Shiro  Tokyo University, hospitals in affiliation with medicine, Speaker, Assistant, 医学部(附属病院), 助教授 (80193027)
SEKI George  Tokyo University, hospitals in affiliation with medicine, Speaker, Assistant, 医学部(附属病院), 助手 (30206619)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥2,600,000 (Direct Cost: ¥2,600,000)
KeywordsNBC-1 / band keratopathy / Cataract / Glaucoma
Research Abstract

Proximal renal tubular acidosis (pRTA) associated with ocular abnormalities such as band keratopathy, cataracts, and glaucoma is caused by mutations in the Na-HCO3 cotransporter (NBC1). To clarify the mechanism by which NBC1 mutations lead to such ocular abnormalities, we performed immunohistochemical analysis of rat and human eyes. The results demonstrated both kidney-type (kNBC1) and a pancreatic type (pNBC1) transporter is present in the corneal endothelium, lens epithelium, and trabecular meshwork cells. We also detected the Na-HCO3 cotransport activity in human lens epithelial (HLE) cells, which was largely inhibited by specific ribozyme against NBC1. These results indicate that the normal transport activity of NBC1 is indispensable for the homeostasis in cornea and lens. NBC1 may also play an important role in regulation of aqueous humor outflow. In the subsequent studies we revealed the transport activity of Na-independent C1/HCO3 exchange activity in HLE cells, which seemed to be related to anion exchanger Aes.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Igarashi T. et al.: "Novel nonsense mutation in the Na^+/HCO_3^-cotransporter gene (SLC_4A_4) in a patient with permanent isolated proximal renal tubular acidosis and bilateral glaucoma"J. Am. Soc. Nophrol.. 12. 713-718 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Igarashi T. et al.: "Unraveling the molecular basis of hereditary renal tubular acidosis"Clin. Exp. Nephrol.. 5. 8-12 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Usui T.et al.: "Molecular basis of ocular abnormalities associated with proximal renal tubular acidosis"J. Clin. Invest.. 108. 107-115 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sun.D.et al.: "Quantifying parphobilinogen deaminase mRNA in microdissected nephron segments by a modified RT-PCR"Kidney Int. 61. 336-341 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Usui, T., Hara, M., Satoh, H., Moriyama, N., Kagaya, H., Amano, S., Oshika, T., Ishii, Y., Ibaraki, N., Hara, C., Kunimi, M., Noiri, E., Tsukamoto, K., Inatomi, J., Kawakami, H., Endo, H., Igarashi, T., Goto, A., Fujita, T., Araie, M., and Seki, G.: J Clin Invest. 108. 107-115 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Igarashi, T., Inatomi, J., Sekine, T., Seki, G., Shimadzu, M., Tozawa, F., Takeshima, Y., Takumi, T., Takahashi, T., Yoshikawa, N., Nakamura, H., and Endo, H.: J Am .Soc Nephrol. 12. 713-718 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Igarashi T, Sekine T, Inatomi J, Seki G: "Unraveling the molecular pathogenesis of isolated proximal renal tubular acidosis."J Am Soc Nephrol. 13. 2171-2177 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Horita S, Zheng Y, Hara C, Yamada H, Kunimi M, Taniguchi S, Uwatoko S, Sugaya T, Goto A, Fujita T, Seki G: "Biphasic regulation of Na+HCO3 cotransporter by angiotensin II type 1A receptor."Hypertension. 40. 707-712 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sun D, Seki G, Uwatoko S, Nakao A, Goto A, Fujita T, Kimura S, Taniguchi S: "Quantifying porphobilinogen deaminase mRNA in microdissected nephron segments by a modified RT-PCR."Kidney Int. 61. 336-341 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Satoh H, Moriyama N, Hara C, Yamada H, Horita S, Kunimi M, Tsukamoto K, Iso N, Inatomi J, Kawakami H, Kudo A, Endo H, Igarashi T, Goto A, Fujita T, Seki G: "Localization of Na+HCO3 cotransporter (NBC-1) variants in rat and human pancreas."Am J Physiol Cell Physiol. 284. C729-C737 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Zheng Yanan, Shoko Horita, Chiaki Hara, Motoei Kunimi, Hideomi Yamada, Takeshi Sugaya, Atsuo Goto, Toshiro Fujita, and George Seki: "Biphasic regulation of renal proximal bicarbonate absorption by luminal AT_<1A> receptor."J Am Soc Nephrol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sun.D et al.: "Quantifying parphobilinorgen deaminase mRNA in microdissected nephran segments by a modified RT-PCR"Kidney Int. 61. 336-341 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Igarashi T et al: "Novel nonsense mutation in Na^+/HCO_3^- contransporter gene(SLC4A4) in a patient with permanent isclated renal tubular acidosis and bilateral glaucome"J.Am.Soc.Nephrol.. 12. 713-718 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Igarashi T et al.: "Unraveling the molecular basis of hereditary renal tubular aeidosis"Clin.Exp.Nephrol.. 5. 8-12 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Usui T et al.: "Molecular basis of ocular abnormalities associated with proximal renal tabular acidosis"J.Clin.Invest.. 108. 107-115 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sun D. et al.: "Quantifying po-phobilinogen deaminase mRNA in microdissocted nephron segments by a modified RT-PCR"Kidney Int.. 61. 336-341 (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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