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

• Published in: Neuroscience research Vol. 65; no. 4; pp. 319 - 325
• Main Authors: Sakai, Yasuhiro, Tanaka, Takayuki, Seki, Masaaki, Okuyama, Shinya, Fukuchi, Takeo, Yamagata, Kanato, Takei, Nobuyuki, Nawa, Hiroyuki, Abe, Haruki
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.12.2009
• Subjects: Animals; Celecoxib; Cell death; Cell Death - drug effects; Cell Death - physiology; Cell survival; COX-2; Cyclooxygenase 2 - drug effects; Cyclooxygenase 2 - genetics; Cyclooxygenase 2 - metabolism; Cyclooxygenase 2 Inhibitors - pharmacology; Cyclooxygenase-2; Data processing; Green Fluorescent Proteins - genetics; Injuries; Ischemia; Knockout mouse; Mice; Mice, Knockout; Mice, Transgenic; Nervous system; Neurodegenerative diseases; Optic nerve; Promoters; Pyrazoles - pharmacology; Reperfusion Injury - metabolism; Reperfusion Injury - pathology; Retina; Retinal ganglion cell; Retinal ganglion cells; Retinal Ganglion Cells - drug effects; Retinal Ganglion Cells - metabolism; Retinal Ganglion Cells - pathology; Sulfonamides - pharmacology; Thy-1 Antigens - genetics; Thy-1-EGFP; Transgenic mice; Transgenic mouse; COX-2; Thy-1-EGFP; Cell death; Knockout mouse; Retina; Transgenic mouse; Retinal ganglion cell
• ISSN: 0168-0102; 1872-8111
• DOI: 10.1016/j.neures.2009.08.008

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.