Inhibition of cyclooxygenase-2 expression by zinc-chelator in retinal ischemia.

Abstract

The zinc ion (Zn2+) is abundant in neurons. However, excessive Zn2+ can induce neuronal cell death. This study examined the role of Zn2+ in transient retinal ischemia in adult male rats. The rats were sacrificed 4-24 h after retinal ischemia by high intra-ocular pressure, and the retinas were prepared for microscopic examination of retinal cell degeneration, and fluorescence microscopy using zinquin ethyl ester as the zinc ion-specific probe. Moreover, COX-2 expression was observed by Western blotting. In control retinas, there was a low Zn2+ concentration in the inner plexiform layer (IPL), a high Zn2+ concentration in the outer plexiform layer (OPL), and no detectable Zn2+ in either the ganglion cell layer (GCL) or the inner nuclear layer (INL). In contrast, in the retinas exposed to ischemia without the administration of the zinc ion chelators (Ca2+-EDTA and TPEN), Zn2+ deposits were found in the IPL and INL beginning 4 h after ischemia and degeneration of neurons was found in the GCL and INL. Less Zn2+ accumulation in the IPL and INL and less neuronal degeneration in the GCL and INL were found in the retinas treated with Ca2+-EDTA or TPEN before ischemia. Furthermore, the COX-2 protein levels increased 4-8 h after retinal ischemia, and chelation of zinc ion inhibited this effect. These results suggest that the accumulation of Zn2+ following an ischemic insult can cause retinal degeneration and induce abnormal COX-2 expression.

• Authors: Jun-Sub Choi, Kyung-A Kim, Yone-Jung Yoon, Takashi Fujikado, Choun-Ki Joo
• Journal: Vision research (Vision Res) Vol. 46 Issue 17 Pg. 2721-7 (Sep 2006) ISSN: 0042-6989 [Print] England
• PMID: 16584753 (Publication Type: Journal Article)

Chemical References

• Chelating Agents
• Cyclooxygenase 2 Inhibitors
• Ethylenediamines
• Edetic Acid
• Cyclooxygenase 2
• Zinc
• N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine

Topics

• Animals
• Chelating Agents (therapeutic use)
• Cyclooxygenase 2 (metabolism)
• Cyclooxygenase 2 Inhibitors (therapeutic use)
• Edetic Acid (therapeutic use)
• Ethylenediamines (therapeutic use)
• Ischemia (complications, enzymology, metabolism)
• Male
• Rats
• Rats, Sprague-Dawley
• Retinal Degeneration (etiology, metabolism, prevention & control)
• Retinal Ganglion Cells (metabolism)
• Retinal Vessels (enzymology, metabolism)
• Zinc (metabolism)