Inhibition of cyclooxygenase-2 expression by zinc-chelator in retinal ischemia.
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.
Choi
Jun-Sub
JS
Department of Ophthalmology and Visual Science, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-ku, Seoul 137-701, Republic of Korea.
Kim
Kyung-A
KA
Yoon
Yone-Jung
YJ
Fujikado
Takashi
T
Joo
Choun-Ki
CK
D000818:Animals; D002614:Chelating Agents / Q000627:therapeutic use; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D004492:Edetic Acid / Q000627:therapeutic use; D005029:Ethylenediamines / Q000627:therapeutic use; D007511:Ischemia / Q000150:complications / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012162:Retinal Degeneration / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D012165:Retinal Ganglion Cells / Q000378:metabolism; D012171:Retinal Vessels / Q000201:enzymology / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism*
D002614:Chelating Agents; D052246:Cyclooxygenase 2 Inhibitors; D005029:Ethylenediamines; D004492:Edetic Acid; D051546:Cyclooxygenase 2; D015032:Zinc; C044387:N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine