Influence of the antioxidants vitamin E and idebenone on retinal cell injury mediated by chemical ischemia, hypoglycemia, or oxidative stress

A role for the antioxidants vitamin E and idebenone in decreasing retinal c ell injury, after metabolic inhibition induced by chemical ischemia and hyp oglycemia, was investigated and compared with oxidative stress conditions. Preincubation of the antioxidants, vitamin E (20 mu M) and idebenone (10 mu M), effectively protected from retinal cell injury after oxidative stress or hypoglycemia, whereas the protection afforded after postincubation of bo th antioxidants was decreased. Delayed retinal cell damage, mediated by che mical ischemia, was attenuated at 10 or 12 b postischemia, only after expos ure to the antioxidants during all the experimental procedure. An antagonis t of the N-methyl-D-aspartate (NMDA) receptors, an inhibitor of nitric oxid e synthase (NOS) or a blocker of L-type Ca2+ channels were ineffective in r educing cell injury induced by chemical ischemia, hypoglycemia or oxidative stress. Oxidative stress and hypoglycemia increased (about 1.7-fold) signi ficantly the fluorescence of the probe DCFH2-DA, that is indicative of intr acellular ROS formation. Free radical generation detected with the probe di hydrorhodamine 123 (DHR 123) was enhanced after oxidative stress, chemical ischemia or hypoglycemia (about 2-fold). Nevertheless, the antioxidants vit amin E or idebenone were ineffective against intracellular ROS generation. Cellular energy charge decreased greatly after chemical ischemia, was moder ately affected after hypoglycemia, but no significant changes were observed after oxidative stress. Preincubation with vitamin E prevented the changes in energy charge upon 6 h posthypoglycemia. We can conclude that irreversi ble changes occurring during chemical ischemia mainly reflect the alteratio ns taking place at the ischemic core, whereas hypoglycemia situations may r eflect changes occurring at the penumbra area, whereby vitamin E or idebeno ne may help to increase cell survival, exerting a beneficial neuroprotectiv e effect. (C) 1999 Elsevier Science Inc.