2021 Fiscal Year Final Research Report
Involvement of tauopathies in optic nerve injuries and therapeutic possibilities through the regulation of mTOR pathway.
Project/Area Number |
19K10002
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 56060:Ophthalmology-related
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Research Institution | Osaka Medical and Pharmaceutical University |
Principal Investigator |
Oku Hidehiro 大阪医科薬科大学, 医学部, 教授 (90177163)
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Co-Investigator(Kenkyū-buntansha) |
小嶌 祥太 大阪医科薬科大学, 医学部, 教授 (10388259)
池田 恒彦 大阪医科薬科大学, 医学部, 名誉教授 (70222891)
喜田 照代 大阪医科薬科大学, 医学部, 教授 (90610105)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Keywords | タウオパチー / 視神経傷害 / オートファジー / 網膜神経節細胞 / P62 |
Outline of Final Research Achievements |
We determined whether tauopathy is associated with impaired autophagy and involved in the death of retinal ganglion cells (RGCs) of rats from an optic nerve crush (ONC). The tau gene siRNA was injected intravitreally to knockdown of tau gene. The effects on neuroprotection were determined by the density of RGCs. The changes in the expressions of phosphorylated tau, P62, and LC3B were determined by immunoblot and immunohistochemistry (IHC). Autophagy was impaired in the retina, as P62 increased by 3.1-fold from that of the control with a reduction of LC3B2/LCB1. There was a 2.1-fold increase of phosphorylated tau in the retina and siTau depressed the increase by 1.3-fold. Expressions of tau and P62 were well co-localized. Pretreatment by siTau showed significant protection of RGCs. Silencing the tau gene is neuroprotective, and tauopathy may be involved in the death of RGCs after ONC. Impaired autophagy may be involved in the ONC-induced tauopathy.
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Free Research Field |
眼科学
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Academic Significance and Societal Importance of the Research Achievements |
tauは中枢神経系の軸索機能維持に必須のタンパクであるが、軸索が傷害されるとリン酸化され重合し、不溶性タンパクとなり神経細胞体に蓄積される特徴を持つ。tauの蓄積から生じる神経変性はタウオパチーと総称されるが、一般には中枢神経系の慢性変性疾患との関連が示唆されている。視神経は網膜神経節細胞の軸索の集合体であるが、緑内障視神経症による網膜神経節細胞死に、tauの蓄積が関与していることが示されていた。本研究の結果、急性の視神経傷害にもタウオパチーが関与していることを示している。様々な視神経疾患を、タウオパチーの関連から研究する必要性が示唆された。
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