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.
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.
Sakai
Yasuhiro
Y
Division of Ophthalmology and Visual Science, Graduate School of Medical and Dental Sciences, Niigata University, 1, Asahimachi, Niigata 951-8585, Japan.
Tanaka
Takayuki
T
Seki
Masaaki
M
Okuyama
Shinya
S
Fukuchi
Takeo
T
Yamagata
Kanato
K
Takei
Nobuyuki
N
Nawa
Hiroyuki
H
Abe
Haruki
H
D000818:Animals; D000068579:Celecoxib; D016923:Cell Death / Q000187:drug effects / Q000502:physiology*; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011720:Pyrazoles / Q000494:pharmacology; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D013449:Sulfonamides / Q000494:pharmacology; D018800:Thy-1 Antigens / Q000235:genetics
D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D018800:Thy-1 Antigens; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D051546:Cyclooxygenase 2; D000068579:Celecoxib