Cyclooxygenase-2 plays a critical role in retinal ganglion cell death after transient ischemia: Real-time monitoring of RGC survival using Thy-1-EGFP transgenic mice

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• 作者：Yasuhiro Sakai ; Takayuki Tanaka ; Masaaki Seki ; Shinya Okuyama ; Takeo Fukuchi ; Kanato Yamagata ; Nobuyuki Takei ; Hiroyuki Nawa ; Haruki Abe
• 关键词：COX-2 ; Thy-1-EGFP ; Retina ; Cell death ; Retinal ganglion cell ; Transgenic mouse ; Knockout mouse
• 刊名：Neuroscience Research
• 出版年：2009
• 出版时间：December 2009
• 年：2009
• 卷：65
• 期：4
• 页码：319-325
• 全文大小：403 K

文摘

The exact role of cyclooxygenase-2 (COX-2) in neurodegeneration of retinal ganglion cells (RGCs) in vivo following ischemia-reperfusion injury of the retina was unknown. We made transgenic mice in which the Thy-1.2 promoter drives the expression of EGFP cDNA (Thy-1-EGFP) in RGCs to monitor RGC survival and death in retinal whole mount preparations and in live animals. We show that celecoxib, a selective COX-2 inhibitor, blocks RGC death after ischemic injury. Furthermore, in COX-2 knockout (COX-2^−/−) mice, RGCs are resistant to ischemia-reperfusion injury. Finally, we performed time-lapse monitoring of RGC death after ischemia in Thy-1-EGFP; COX-2^−/− mice. Our data show that COX-2 plays a crucial role in ischemia-reperfusion injury-induced RGC death. Inhibition of COX-2 activity may therefore be an effective therapy for neurodegenerative diseases of the retina and optic nerve.