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Establishment of neuroprotective and regenerative therapies for neuronal degeneration of diabetic retinopathy

Research Project

Project/Area Number 25462751
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Ophthalmology
Research InstitutionChiba University

Principal Investigator

Oshitari Toshiyuki  千葉大学, 医学(系)研究科(研究院), 講師 (40546769)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsRGC neuropathy / 糖尿病網膜症 / 神経保護 / 神経突起再生 / neurotorphin-4 / NF-kB / SP1 / 網膜3次元培養 / neurotrophin-4 / 神経血管単位 / TUDCA / 終末糖化産物
Outline of Final Research Achievements

Neuronal abnormalities of diabetic retinopathy are irreversible changes and accumulated below the surface. These changes are directly related to permanent vision loss. RGC neuropathy is a progressive optic nerve neuropathy with RGC death and axonal degeneration in diabetic patients. Thus, neuroprotective and regenerative therapies that inhibit the progression of RGC loss and axonal degeneration are greatly required. For these purpose, we used three-dimensional collagen gel culture of rat retinas. Retinal explants were incubated with AGEs simultaneously supplemented with NT-4, HGF, GDNF, and TUDCA. In retinas supplemented with NT-4, the number of regenerating neurites were the most among all groups. In addition, immunopositivities of NF-kB, SP1, JNK and p38 were increased in retinas incubated with AGEs, and decreased in retinas with AGEs supplemented with neurotrophic factors. These results indicate that NF-kB, JNK and p38 are proapoptotic factors in diabetic retinal neurons.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (22 results)

All 2015 2014 2013

All Journal Article (14 results) (of which Peer Reviewed: 14 results,  Open Access: 8 results,  Acknowledgement Compliant: 8 results) Presentation (8 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Altered expression of NF-kB and SP1 after exposure to advanced glycation end-products and effects of neurotrophic factors in AGEs exposed rat retinas2015

    • Author(s)
      Guzel Bikbova, Toshiyuki Oshitari, Takayuki Baba, Shuichi Yamamoto
    • Journal Title

      Journal of Diabetes Research

      Volume: 2015 Pages: 1-11

    • DOI

      10.1155/2015/543818

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Level of vitreous alpha-B crystallin in eyes with rhegmatogenous retinal detachment2015

    • Author(s)
      Takayuki Baba, Toshiyuki Oshitari, Shuichi Yamamoto
    • Journal Title

      Graefes Arch Clin Exp Ophthalmol

      Volume: 253 Issue: 8 Pages: 1251-1254

    • DOI

      10.1007/s00417-014-2815-z

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Neurovascular protection instead of only neuroprotetion2015

    • Author(s)
      Toshiyuki Oshitari
    • Journal Title

      Edorium Journal of Ophthalmology

      Volume: 1 Issue: 2 Pages: 1-3

    • DOI

      10.5348/o02-2015-1-ed-1

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Risk factors for refractory diabetic macular edema after sub-tenon's capsule triamcinolone acetone injection2015

    • Author(s)
      Toshiyuki Oshitari, Yuta Kitamura, Sakiko Nonomura, Miyuki Arai, Yoko Takatsuna, Eiju Sato, Takayuki Baba, Shuichi Yamamoto
    • Journal Title

      Journal of Ophthalmology

      Volume: 2015 Pages: 1-4

    • DOI

      10.1155/2015/195737

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Effects of sub-Tenon's capsule triamcinolone acetonide injection combined with micro aneurysm photocoagulation on diabetic macular edema2015

    • Author(s)
      Toshiyuki Oshitari, Sakiko Nonomura, Miyuki Arai, Yoko Takatsuna, Eiju Sato, Takayuki Baba, Shuichi Yamamoto
    • Journal Title

      International Medical Case Reports Journal

      Volume: 8 Pages: 321-326

    • DOI

      10.2147/imcrj.s89970

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Neurotrophic factors for retinal ganglion cell neuropathy-with a special reference to diabetic neuropathy in the retina2014

    • Author(s)
      Guzel Bikbova, Toshiyuki Oshitari, Takayuki Baba, Shuichi Yamamoto
    • Journal Title

      Current Diabetes Reviews

      Volume: 10 Pages: 166-176

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Correlation between Fourier-Domain optical coherence tomography parameters and HbA1c level and diabetes duration in early stage diabetic retinopathy2014

    • Author(s)
      Toshiyuki Oshitari, Sakiko Nonomura, Miyuki Arai, Takayuki Baba, Shuichi Yamamoto
    • Journal Title

      Austin Journal of Clinical Ophthalmology

      Volume: 1

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Neuronal cell death and regeneration in diseases associated with AGEs accumulation: perspectives2014

    • Author(s)
      Guzel Bikbova, Toshiyuki Oshitari, Shuichi Yamamoto
    • Journal Title

      Neural Regeneration Research

      Volume: 9 Pages: 701-702

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] The effect of sub-Tenon's capsule triamcinolone acetone injection to that of pars plana vitrectomy for diabetic macular edema2014

    • Author(s)
      Sakiko Nonomura, Toshiyuki Oshitari, Miyuki Arai, Eiju Sato, Yoko Takatsuna, Takayuki Baba, Shuichi Yamamoto
    • Journal Title

      Clinical Ophthalmology

      Volume: 8 Pages: 825-830

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Werner syndrome with refractory cystoid macular edema and immunohistochemical analysis of WRN proteins in human retinas.2014

    • Author(s)
      Oshitari T, Kitahashi M, Mizuno S, Baba T, Kubota-Taniai M, Takemoto M, Yokote K, Yamamoto S, Roy S
    • Journal Title

      BMC Ophthalmol.

      Volume: - Issue: 1 Pages: 31-31

    • DOI

      10.1186/1471-2415-14-31

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Level of Vascular Endothelial Growth Factor 165b in Human Aqueous Humor2014

    • Author(s)
      Baba T, Bikbova G, Kitahashi M, Yokouchi H, Oshirtari T, Yamamoto S
    • Journal Title

      Current Eye Research

      Volume: in print Issue: 8 Pages: 830-836

    • DOI

      10.3109/02713683.2013.877935

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Increased expression of c-Fos, c-Jun, c-Jun-N-terminal kinase associated with neuronal cell death in retinas of diabetic patients2014

    • Author(s)
      Toshiyuki Oshitari, Shuichi Yamamoto, Sayon Roy
    • Journal Title

      Current Eye Research

      Volume: 39 Issue: 5 Pages: 527-531

    • DOI

      10.3109/02713683.2013.833248

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Increased expression of phosphorylated c-Jun and phosphorylated c-Jun N-terminal kinase associated with neuronal cell death in diabetic and high glucose exposed rat retinas2014

    • Author(s)
      Toshiyuki Oshitari, Guzel Bikbova, Shuichi Yamamoto
    • Journal Title

      Brain Research Bulletin

      Volume: 101 Pages: 18-25

    • DOI

      10.1016/j.brainresbull.2013.12.002

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Neurite regeneration in adult rat retinas exposed to advanced glycation end-products and regenerative effects of neurotrophin-42013

    • Author(s)
      Guzel Bikbova, Toshiyuki Oshitari, Shuichi Yamamoto
    • Journal Title

      Brain Research

      Volume: 1534 Pages: 33-45

    • DOI

      10.1016/j.brainres.2013.08.027

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Transcription factors involved in cell death and regeneration in AGEs exposed retinal neurons2015

    • Author(s)
      Toshiyuki Oshitari, Guzel Bikbova, Shuichi Yamamoto
    • Organizer
      European Association for Vision and Eye Research 2015
    • Place of Presentation
      Nice, France
    • Year and Date
      2015-10-07
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] JNK and p38 expression involved in regenerative effect of different neurotrophic factors in rat retinas exposed to AGEs2015

    • Author(s)
      Guzel Bikbova, Toshiyuki Oshitari, Shuichi Yamamoto
    • Organizer
      Association of Research in Vision and Ophthalmology Annual Meeting 2015
    • Place of Presentation
      Denver, Colo, USA
    • Year and Date
      2015-05-03
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Advanced glycation end-products induced activation of NF-kB and its suppression by different neurotrophic factors2014

    • Author(s)
      Guzel Bikbova, Toshiyuki Oshitari, Shuichi Yamamoto
    • Organizer
      XXI Biennial Meeting of the ISER 2104
    • Place of Presentation
      Nice, France
    • Year and Date
      2014-10-01 – 2014-10-04
    • Related Report
      2014 Research-status Report
  • [Presentation] Regenerative effect of taurine-conjugated ursodeoxycholic acid and neurotrophic-4 in rat retinas exposed to high glucose2014

    • Author(s)
      Toshiyuki Oshitari, Guzel Bikbova, Shuichi Yamamoto
    • Organizer
      XXI Biennial Meeting of the ISER 2104
    • Place of Presentation
      San Francisco, CA, USA
    • Year and Date
      2014-07-20 – 2014-07-24
    • Related Report
      2014 Research-status Report
  • [Presentation] Neurite regeneration in adult rat retinas exposed to low dose advanced glycation end-products and regenerative effects of neurotrophin-42014

    • Author(s)
      Guzel Bikbova, Toshiyuki Oshitari, Shuichi Yamamoto
    • Organizer
      XXI Biennial Meeting of the ISER 2104
    • Place of Presentation
      San Francisco, CA, USA
    • Year and Date
      2014-07-20 – 2014-07-24
    • Related Report
      2014 Research-status Report
  • [Presentation] Neuroprotective and regenerative effect of taurine-conjugated ursodeoxycholic acid in rat retinas exposed to high glucose2014

    • Author(s)
      Toshiyuki Oshitari, Guzel Bikbova, Shuichi Yamamoto
    • Organizer
      ARVO2014
    • Place of Presentation
      Orlando, Florida, USA
    • Year and Date
      2014-05-04 – 2014-05-08
    • Related Report
      2014 Research-status Report
  • [Presentation] Comparison of regenerative effect of tauroursodeoxycholic acid with neurotrophin-4 in high glucose exposed rat retinas2014

    • Author(s)
      Toshiyuki Oshitari, Guzel Bikbova, Shuichi Yamamoto
    • Organizer
      WOC2014
    • Place of Presentation
      Tokyo
    • Related Report
      2013 Research-status Report
  • [Presentation] In neuronal cell death of AGE-exposed rat retinas both caspase-dependent and independent cell death pathways are involved2014

    • Author(s)
      Guzel Bikbova, Toshiyuki Oshitari, Shuichi Yamamoto
    • Organizer
      WOC2014
    • Place of Presentation
      Tokyo
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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