Ferulic acid, but not tetramethylpyrazine, significantly attenuates retinal ischemia/reperfusion-induced alterations by acting as a hydroxyl radical scavenger.
OBJECTIVE
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 tetramethylpyrazine, 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.
Chao
Hsiao-Ming
HM
Department of Ophthalmology, Veterans General Hospital, Taipei, Taiwan, ROC. hsiao-ming.chao@vghtpe.gov.tw
Lin
De-Ean
DE
Chang
Ying
Y
Hsu
Weng-Ming
WM
Lee
Shui-Mei
SM
Lee
Fenq-Lih
FL
Chi
Chin-Wen
CW
Pan
Wynn H T
WH
Liu
Tsung-Yun
TY
Lui
Wing-Yiu
WY
Ho
Low-Tone
LT
Kuo
Cheng-Deng
CD
Chan
Chia-Chin
CC
Chao
Fang-Ping
FP
D000818:Animals; D003373:Coumaric Acids / Q000494:pharmacology* / Q000627:therapeutic use; D004596:Electroretinography; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use; D017665:Hydroxyl Radical / Q000378:metabolism; D007150:Immunohistochemistry; D007511:Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D011719:Pyrazines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012160:Retina / Q000187:drug effects* / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D003373:Coumaric Acids; D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D011719:Pyrazines; D017382:Reactive Oxygen Species; D017665:Hydroxyl Radical; C004999:ferulic acid; C017953:tetramethylpyrazine