Alpha-lipoic acid protects the retina against ischemia-reperfusion.
The aim of this study was to examine whether the antioxidant alpha-lipoic acid protects retinal neurons from ischemia-reperfusion injury. Rats were injected intraperitoneally with either vehicle or alpha-lipoic acid (100 mg/kg) once daily for 11 days. On the third day, ischemia was delivered to the rat retina by raising the intraocular pressure above systolic blood pressure for 45 min. The electroretinogram was measured prior to ischemia and 5 days after reperfusion. Rats were killed 5 or 8 days after reperfusion and the retinas were processed for immunohistochemistry and for determination of mRNA levels by RT-PCR. Ischemia-reperfusion caused a significant reduction of the a- and b-wave amplitudes of the electroretinogram, a decrease in nitric oxide synthase and Thy-1 immunoreactivities, a decrease of retinal ganglion cell-specific mRNAs and an increase in bFGF and CNTF mRNA levels. All of these changes were clearly counteracted by alpha-lipoic acid. Moreover, in mixed rat retinal cultures, alpha-lipoic acid partially counteracted the loss of GABA-immunoreactive neurons induced by anoxia. The results of the study demonstrate that alpha-lipoic acid provides protection to the retina as a whole, and to ganglion cells in particular, from ischemia-reperfusion injuries. alpha-Lipoic acid also displayed negligible affinity for voltage-dependent sodium and calcium channels.
Chidlow
G
G
Nuffield Laboratory of Ophthalmology, University of Oxford, Walton Street, Oxford OX2 6AW, UK.
Schmidt
K-G
KG
Wood
J P M
JP
Melena
J
J
Osborne
N N
NN
D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001667:Binding, Competitive; D019208:Brain-Derived Neurotrophic Factor / Q000187:drug effects / Q000235:genetics; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics; D002478:Cells, Cultured; D020934:Ciliary Neurotrophic Factor / Q000187:drug effects / Q000235:genetics; D017931:DNA Primers; D004110:Diltiazem / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004596:Electroretinography / Q000187:drug effects; D005346:Fibroblast Growth Factors / Q000187:drug effects / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000187:drug effects / Q000235:genetics; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000187:drug effects / Q000378:metabolism; D016202:N-Methylaspartate / Q000494:pharmacology; D009543:Nifedipine / Q000493:pharmacokinetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D012164:Retinal Diseases / Q000188:drug therapy* / Q000503:physiopathology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012243:Rhodopsin / Q000187:drug effects / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D008063:Thioctic Acid / Q000627:therapeutic use*; D018800:Thy-1 Antigens / Q000378:metabolism; D014701:Veratridine / Q000494:pharmacology
D000779:Anesthetics, Local; D000975:Antioxidants; D019208:Brain-Derived Neurotrophic Factor; D002121:Calcium Channel Blockers; D020934:Ciliary Neurotrophic Factor; D017931:DNA Primers; D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger; D018800:Thy-1 Antigens; D013779:Tetrodotoxin; D005346:Fibroblast Growth Factors; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D014701:Veratridine; D008063:Thioctic Acid; D012243:Rhodopsin; D012964:Sodium; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D004110:Diltiazem; D009543:Nifedipine; D002118:Calcium