Involvement of oxygen free radicals in experimental retinal ischemia and the selective vulnerability of retinal damage.
Protective effects of CV-3611, a free radical scavenger, on retinal ischemic injury in the rat and on glutamate-induced cytotoxicity in a cell line were evaluated. Transient retinal ischemia was induced by raising intraocular pressure of rats to 110 mm Hg for 45 min, and the electroretinogram (ERG) was measured to evaluate retinal function. No ERG could be recorded immediately after reperfusion, and thereafter the ERG gradually recovered. Recovery of the a-wave latency and the amplitudes of the a and b waves in the CV-3611-treated (10 mg/kg, p.o.) group were significantly better than those in the control group up to 24 h after reperfusion. In both the control and CV-3611 group, the b wave showed better recovery than the a wave up to 6 h after reperfusion, while the relationship was reversed after 24-hour reperfusion. Glutamate (10 mM)-induced cytotoxicity in the N18-RE-105 cell, a neural retina-neuroblastoma hybridoma, was quantified by measuring lactate dehydrogenase. Three and 10 microM of CV-3611 significantly attenuated the glutamate-induced cytotoxicity in N18-RE-105 cells. Thus, the radical scavenger (CV-3611) promoted the recovery of retinal function after ischemia-reperfusion injury and ameliorated glutamate-induced cytotoxicity. These results suggest that oxygen free radicals play an important role in the early phase of retinal ischemic injury. Moreover, differential recovery processes of the a and b waves after ischemia suggest that the selective vulnerability of the retina to ischemia could change functionally during the period of reperfusion.
Kuriyama
H
H
Department of Life Science, Himeji Institute of Technology, Harima Science Garden City, Akoh-gun, Hyogo 678-1297, Japan.
Waki
M
M
Nakagawa
M
M
Tsuda
M
M
D000818:Animals; D001205:Ascorbic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D002460:Cell Line; D004596:Electroretinography; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005609:Free Radicals / Q000378:metabolism; D018698:Glutamic Acid / Q000633:toxicity; D006825:Hybridomas / Q000187:drug effects / Q000378:metabolism; D007429:Intraocular Pressure; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D051379:Mice; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D012164:Retinal Diseases / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*
D016166:Free Radical Scavengers; D005609:Free Radicals; D018698:Glutamic Acid; C061185:2-O-octadecylascorbic acid; D007770:L-Lactate Dehydrogenase; D001205:Ascorbic Acid; D010100:Oxygen