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Molecular Mechanisms of Damage to Retinal Neuronal Cells in Diabetic Retinopathy and New Therapeutic Modalities

Molecular Mechanisms of Damage to Retinal Neuronal Cells in Diabetic Retinopathy and New Therapeutic Modalities
糖尿病视网膜病变视网膜神经细胞损伤的分子机制及新的治疗方式
批准号:
17591819
负责人:
YAMASHITA Hidetoshi
金额:
$2.24万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (C)
财政年份:
2005
资助国家:
日本
项目状态:
已结题
起止时间:
2005 至 2006

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中文摘要
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英文摘要
Diabetic retinopathy remains a significant cause of acquired visual loss in working-age adults worldwide. The incidence of diabetic retinopathy increases along with the increase of the number of diabetes mellitus patients, and it is mandatory to develop the new strategy of the protection of retinal neuronal cells to decrease the number of acquired visual loss patients due to diabetic retinopathy. To inquire this strategy, we have investigated the molecular mechanisms of the damage to retinal neuronal cells and to inhibit this process.We clarified that the activation of protein kinase C β (PKC β ) and diacylglycerol kinase (DGK) contribute to the development and progression of diabetic retinopathy by affecting the retinal neuronal cells. The exposure to the high glucose level leaded to the de novo increase in the synthesis of diacylglycerol (DAG), which activated PKC β3 in the retinal neuronal cells and accelerated the production of vascular endothelial growth factor (VEGF). DGK catalyz … More es phosphorylation of DAG to phosphatidic acid (PA), controls DAG levels, and was stimulated after the exposure to the high glucose. We clarified that DGK a was related to the pathogenesis of diabetic retinopathy through VEGF expression both in 2 types of retinoblastoma cells and the retina of streptozotocin-induced diabetic rats as an animal model. In the pathogenesis of diabetic retinopathy, fibro-vascular membrane formation is important, and hyalocytes are involved in this process. We observed the expression of VEGF and interleukin6 (IL-6) was stimulated by the inflammatory cytokines (IL-1 α and β3, TNF-α ).The mechanisms of retinal neuronal cell death : ActivinA is expressed in eyes and exerts certain effects on retinopathy. The effects of activinA on retinal neuronal cells were investigated using retinoblastoma (RB) cell lines. RB cell lines were used as the undifferentiated retinal cells, expressed activin receptors and cytoplasmic components for activin. The signal transduction pathway was confirmed by using Luciferase assay after the stimulation of activinA. Activin A signal was shown to induce apoptosis in RB cells. Taken together, high glucose condition and/or various cytokines may be related to the retinal neuronal cell damage including apoptosis. The inhibition of apoptosis may be the target to protect retinal neuronal cells. Less
期刊论文(19)
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糖尿病網膜症の病期と治療。
糖尿病视网膜病变的阶段和治疗。
DOI: --
发表时间: 2006
期刊: カレントテラピー 24巻11号
影响因子: --
作者: [中野早紀子, 山本禎子, 山下英俊]
通讯作者: 山下英俊
OCT光干渉断層計2機種による網膜厚マッププログラム測定の比較。
使用两种类型的 OCT 光学相干断层扫描进行视网膜厚度图程序测量的比较。
DOI: --
发表时间: 2005
期刊: 臨床眼科 59
影响因子: --
作者: [川崎良, 土谷大仁朗, 芳賀真理江, 神尾聡美, 佐藤浩章, 菅野誠, 山本禎子, 山下英俊]
通讯作者: 山下英俊
DOI: --
发表时间: 2005
期刊: 日本臨床(63巻増刊号6。糖尿病性細小血管症-基礎・臨床のアツプデートーー) 63巻6号
影响因子: --
作者: [山下英俊, 山本禎子]
通讯作者: 山本禎子
「研究成果報告書概要(欧文)」より
摘自《研究结果报告摘要(欧洲)》
DOI: --
发表时间: 2006
期刊: Seibutsu Butsuri 46(1)
影响因子: --
作者: [Yasushi Shigeri, Keiko Shimamoto]
通讯作者: Keiko Shimamoto
14
    Comprehensive Social Scientific Study on Radioactive Waste Disposal Issues
    • 批准号:
      19H04335
    • 项目类别:
      Grant-in-Aid for Scientific Research (B)
    • 资助金额:
      $9.4万
    • 财政年份:
      2019
    • 负责人:
      YAMASHITA Hidetoshi
    • 依托单位:
    Molecular epidemiological study on choroidopathy in diabetic eyes
    • 批准号:
      18K09439
    • 项目类别:
      Grant-in-Aid for Scientific Research (C)
    • 资助金额:
      $2.91万
    • 财政年份:
      2018
    • 负责人:
      YAMASHITA Hidetoshi
    • 依托单位:
    Molecular mechanisms of progression of diabetic retinopathy focusing inflammatory mechanisms by dendritic cells in vitreous
    • 批准号:
      15K10832
    • 项目类别:
      Grant-in-Aid for Scientific Research (C)
    • 资助金额:
      $3.08万
    • 财政年份:
      2015
    • 负责人:
      YAMASHITA Hidetoshi
    • 依托单位:
    Research on policies for the promotion of locally initiated renewable energy projects
    • 批准号:
      25281068
    • 项目类别:
      Grant-in-Aid for Scientific Research (B)
    • 资助金额:
      $11.4万
    • 财政年份:
      2013
    • 负责人:
      YAMASHITA Hidetoshi
    • 依托单位:
    海外基金