Tumor necrosis factor-α mediates oligodendrocyte death and delayed retinal ganglion cell loss in a mouse model of glaucoma

Toru Nakazawa, Chifuyu Nakazawa, Akihisa Matsubara, Kousuke Noda, Toshio Hisatomi, Haicheng She, Norman Michaud, Ali Hafezi-Moghadam, Joan W. Miller, Larry I. Benowitz

研究成果: Article査読

333 被引用数 (Scopus)

抄録

Glaucoma is a widespread ocular disease characterized by a progressive loss of retinal ganglion cells (RGCs). Previous studies suggest that the cytokine tumor necrosis factor-α(TNF-α) may contribute to the disease process, although its role in vivo and its mechanism of action are unclear. To investigate pathophysiological mechanisms in glaucoma, we induced ocular hypertension (OH) in mice by angle closure via laser irradiation. This treatment resulted in a rapid upregulation of TNF-α, followed sequentially by microglial activation, loss of optic nerve oligodendrocytes, and delayed loss of RGCs. Intravitreal TNF-α injections in normal mice mimicked these effects. Conversely, an anti-TNF-α-neutralizing antibody or deleting the genes encoding TNF-αor its receptor, TNFR2, blocked the deleterious effects of OH. Deleting the CD11b/CD18 gene prevented microglial activation and also blocked the pathophysiological effects of OH. Thus TNF-α provides an essential, although indirect, link between OH and RGCloss in vivo. Blocking TNF-α signaling or inflammation, therefore,may be helpful in treating glaucoma.

本文言語English
ページ(範囲)12633-12641
ページ数9
ジャーナルJournal of Neuroscience
26
49
DOI
出版ステータスPublished - 2006 12月 6

ASJC Scopus subject areas

  • 神経科学(全般)

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