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S.–I. Kawai, H. Murakami, K. Sato, A. Noiri, K. Kawai, M. Sakurai; Suppression of Rat Retinal Ganglion Cells Degeneration Following Retinal Ischemia/Reperfusion Injury, Using Edaravone and EUK–189, The Free Radical Scavenger . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1575.
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© ARVO (1962-2015); The Authors (2016-present)
We have recently reported that the neurodegeneration of rat retinal ganglion cells (RGCs) in acute phase of ischemia/reperfusion (I/R) injury occurs due to reactive oxygen species (ROS). The purpose of this study is to report which ROS was implicated in the susceptibility of rat RGCs with I/R injury, using edaravone (ED), a scavenger of hydrogen peroxide radical, and EUK–189, a catalytic antioxidant that scavenges the super oxide anion and hydrogen peroxide.
Retinal ischemia, caused by transient elevation of intraocular pressure above systolic pressure (110mmHg) for 75 minutes by intraocular cannulation, was studied in Wistar rats. The neuroprotective effect of ED and EUK–189 was investigated several timing of intraperitoneal injection (0.5, 1, 2, 3, 6, 12 hours of reperfusion). After reperfusion, loss of RGCs was determined quantitatively by retrograde labeling with Fluoro–Gold. The western blot analysis for COX–1, COX–2, iNOS, and BCL–x were also examined in several length of reperfusion (0.5h, 1h, 2h, 3h, 6h, 12h, 1d, 3d, 5d, 7d) for confirming whether RGC degeneration was due to apoptosis or necrosis.
Six hours after ischemia, treatment with both EUK–189 and ED significantly reduced the loss of RGCs compared with serine control (28.7±5.2% cell loss)(P<0.05). EUK–189 (17.6±4.3% cell loss) was more effective than ED (22.3±3.8% cell loss). Regarding the peak of drug effect, EUK–189 (0.5h reperfusion) affects earlier than ED (3h reperfusion). There was no synergistic effect of ED and EUK–189. In western blot analysis, COX–1 was found every time point as constitutive protein. COX–2 increased in 30min, 1h, 2h, 3h, and 6h after ischemia. iNOS did not amplify within 3h after ischemia, then increased afterward 6h and remain until 7days reperfusion. BCL–x was slightly found in 12, 24 and 72h after ischemia.
Both drugs have intensive neuroprotective effect, EUK–189 affects immediately after ischemia, and ED affects 3 to 12 hours after ischemia. Our results suggest that super oxide anion play a very important role of primary retinal damaging process for ischemia/reperfusion injury in rat. Furthermore, free radical scavenger might be helpful to protect RGCs on acute phase of ischemic conditions in the eye.
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