Ferulic acid, but not tetramethylpyrazine, significantly attenuates retinal ischemia/reperfusion-induced alterations by acting as a hydroxyl radical scavenger

Purpose: Ischemia plays an important role in glaucomatous optic neuropathy and retinal vascular occlusive disorders, which renders investigation vital. Methods: Retinal ischemia was induced by raising intraocular pressure to 120 mmHg. Its mechanism and management was evaluated by measuring ^.OH levels, electroretinogram (ERG) b-wave amplitudes, immunohisto-chemistry, and reverse transcriptase polymerase chain reaction. Results: Ischemia for 45, 60, and 75 min caused significant and time-dependent increased ^.OH levels, which might contribute to retinal ischemic injures. Specifically, 60 min of ischemia plus reperfusion, causing moderate oxidative stress, resulted in retinal changes that were characterized by decreased ERG b-wave amplitudes, loss of choline acetyltransferase immunolabeled amacrine cell bodies/neuronal processes, downregulated Thy-1 m-RNA levels (indexing retinal ganglion cells; RGCs), and reduced thickness of the Thy-1 immunolabeled RGC and inner plexiform layers. Of clinical importance, this is the first study to show that ischemic detrimental effects are significantly blunted when 0.5 nmol of ferulic acid, one active ingredient of Ligusticum walliichi (Chuanxiong), was applied 24 h before retinal ischemia. Further, but not to a significant level, 0.5 nmole of tetramethylpyazine, another Chuanxiong-active component, showed such an ameliorating trend. Moreover, the 60-min ischemia-induced significant increase in ^.OH production was significantly attenuated by FA. Conclusions: FA is able to protect against retinal ischemia and possibly glaucoma by, at least in part, acting as a ^.OH scavenger.