Increased activity of cyclooxygenase-2 signals early neurodegenerative events in the rat retina following transient ischemia.

Abstract

Following transient retinal ischemia, there is neuronal cell death, breakdown of the blood-retinal barrier, activation of microglia and infiltration by hematogenous cells. The early appearance of cyclooxygenase-2 (COX-2) following an ischemic event may be responsible for signaling some of the responses that lead to neurodegeneration. We have determined the time courses of changes in protein levels and cellular localizations of COX-2 in the rat retina after transient ischemia. In the normal rat retina, COX-2 immunoreactivity was present in neurons in the INL and ganglion cell layer (GCL). Six to 12 hr after ischemia, COX-2 immunoreactivity was upregulated/induced in horizontal cells, amacrine cells, retinal ganglion cells, displaced amacrine cells of the INL and GCL, and Müller cells. The NMDA-receptor antagonist, MK801, blocked the increased COX-2 protein level and COX-2 immunoreactivity in neurons of the INL and GCL, but did not affect the induction of COX-2 in Müller cells after ischemia. The selective COX-2 inhibitor, SC-58236, prevented apoptotic cell death and was neuroprotective against loss of retinal ganglion cells after ischemia. Following transient ischemia, the selective COX-2 inhibitor did not prevent breakdown of the blood-retinal barrier or activation of microglia. However, the selective COX-2 inhibitor reduced infiltration of hematogenous cells into the retina. These results suggest that the early, increased activity of COX-2 signals neurodegenerative events following retinal ischemia.

• Authors: Won-Kyu Ju, Keun-Young Kim, Arthur H Neufeld
• Journal: Experimental eye research (Exp Eye Res) Vol. 77 Issue 2 Pg. 137-45 (Aug 2003) ISSN: 0014-4835 [Print] England
• PMID: 12873443 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• 4-(5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide
• Cyclooxygenase 2 Inhibitors
• Cyclooxygenase Inhibitors
• Excitatory Amino Acid Antagonists
• Isoenzymes
• Pyrazoles
• Sulfonamides
• Dizocilpine Maleate
• Cyclooxygenase 2
• Prostaglandin-Endoperoxide Synthases

Topics

• Animals
• Blood-Retinal Barrier
• Cyclooxygenase 2
• Cyclooxygenase 2 Inhibitors
• Cyclooxygenase Inhibitors (pharmacology)
• Dizocilpine Maleate (pharmacology)
• Excitatory Amino Acid Antagonists (pharmacology)
• Immunohistochemistry (methods)
• In Situ Nick-End Labeling
• Ischemia (enzymology)
• Isoenzymes (antagonists & inhibitors, metabolism)
• Male
• Microglia
• Prostaglandin-Endoperoxide Synthases (metabolism)
• Pyrazoles
• Rats
• Rats, Wistar
• Retinal Diseases (enzymology)
• Retinal Ganglion Cells (enzymology)
• Retinal Vessels
• Sulfonamides
• Up-Regulation