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論文
- タイトル
- タイトル（英）
- Microglia mediate non-cell-autonomous cell death of retinal ganglion cells.
- 参照URL
- https://researchmap.jp/read0091842/published_papers/17419356
- 著者
- 著者（英）
- Akiko Takeda,Youichi Shinozaki,Kenji Kashiwagi,Nobuhiko Ohno,Kei Eto,Hiroaki Wake,Junichi Nabekura,Schuichi Koizumi
- 担当区分
- 概要
- 概要（英）
- Excitotoxicity is well known in the neuronal death in the brain and is also linked to neuronal damages in the retina. Recent accumulating evidence show that microglia greatly affect excitotoxicity in the brain, but their roles in retina have received only limited attention. Here, we report that retinal excitotoxicity is mediated by microglia. To this end, we employed three discrete methods, that is, pharmacological inhibition of microglia by minocycline, pharmacological ablation by an antagonist for colony stimulating factor 1 receptor (PLX5622), and genetic ablation of microglia using Iba1-tTA::DTAtetO/tetO mice. Intravitreal injection of NMDA increased the number of apoptotic retinal ganglion cells (RGCs) followed by reduction in the number of RGCs. Although microglia did not respond to NMDA directly, they became reactive earlier than RGC damages. Inhibition or ablation of microglia protected RGCs against NMDA. We found up-regulation of proinflammatory cytokine genes including Il1b, Il6 and Tnfa, among which Tnfa was selectively blocked by minocycline. PLX5622 also suppressed Tnfa expression. Tumor necrosis factor α (TNFα) signals were restricted in microglia at very early followed by spreading into other cell types. TNFα up-regulation in microglia and other cells were significantly attenuated by minocycline and PLX5622, suggesting a central role of microglia for TNFα induction. Both inhibition of TNFα and knockdown of TNF receptor type 1 by siRNA protected RGCs against NMDA. Taken together, our data demonstrate that a phenotypic change of microglia into a neurotoxic one is a critical event for the NMDA-induced degeneration of RGCs, suggesting an importance of non-cell-autonomous mechanism in the retinal neuronal excitotoxicity.
- 出版者・発行元
- 出版者・発行元（英）
- 誌名
- 誌名（英）
- Glia
- 巻
- 66
- 号
- 11
- 開始ページ
- 2366
- 終了ページ
- 2384
- 出版年月
- 2018年11月
- 査読の有無
- 査読有り
- 招待の有無
- 掲載種別
- 研究論文（学術雑誌）
- ISSN
- 0894-1491
- DOI URL
- https://doi.org/10.1002/glia.23475
- 共同研究・競争的資金等の研究課題
研究者
篠﨑 陽一
(シノザキ ヨウイチ)