Deleterious role of TNF-α in retinal ischemia-reperfusion injury

被引：65

作者：

Berger, Samuel ^{[1
]}

Savitz, Sean I. ^{[2
]}

Nijhawan, Sheetal ^{[1
]}

Singh, Manjeet ^{[1
]}

David, Joel ^{[1
]}

Rosenbaum, Pearl S. ^{[3
,4
]}

Rosenbaum, Daniel M. ^{[1
]}

机构：

[1] Suny Downstate Med Ctr, Dept Neurol, Brooklyn, NY 11203 USA

[2] Univ Texas Houston, Sch Med, Dept Neurol, Houston, TX USA

[3] Albert Einstein Coll Med, Montefiore Med Ctr, Dept Pathol, Bronx, NY 10467 USA

[4] Albert Einstein Coll Med, Bronx Lebanon Hosp Ctr, Dept Ophthalmol, Bronx, NY 10467 USA

来源：

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE | 2008年 / 49卷 / 08期

关键词：

D O I：

10.1167/iovs.07-0817

中图分类号：

R77 [眼科学];

学科分类号：

100212 ;

摘要：

PURPOSE. Tumor necrosis factor (TNF)-alpha is a mediator of neuronal cell death and survival in ischemia-reperfusion injury. This study was conducted to further elucidate the role of TNF-alpha and its receptor in an in vivo model of retinal ischemia reperfusion injury by investigating its effects on retinal histopathology and function. METHODS. Retinal ischemia-reperfusion injury was performed on p55 and p75 knockout (KO) mice and Sprague-Dawley rats using the high intraocular pressure method. The temporal expression of TNF-alpha was ascertained with immunohistochemical staining. Separate rats received intravitreal recombinant TNF-alpha or neutralizing antibody before or after ischemia. TUNEL labeling was performed to assess for cell death, and electroretinography was performed to assess function. RESULTS. TNF-alpha expression peaked at 12 to 24 hours after ischemia-reperfusion injury. TUNEL staining was diminished after intravitreal TNF-alpha antibody. Both transgenic KOs demonstrated significantly less functional impairment. Rats receiving recombinant TNF-alpha 48 hours after ischemia showed exaggerated functional impairment. Animals treated with TNF-alpha antibody before ischemia displayed significant functional improvement. CONCLUSIONS. TNF-alpha plays a largely deleterious role in ischemia -reperfusion injury in an in vivo model of retinal injury. Direct neutralization of this cytokine partially preserves retinal function. The diverse characteristics of TNF-alpha are attributed in part to the timing of its expression after injury. TNF-alpha receptor expression and function, along with combination treatments targeting death receptor-mediated apoptosis, should be further explored to develop neuroprotective therapeutic strategies for acute retinal ischemic disorders.

引用

页码：3605 / 3610

页数：6

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