GABA agonists fail to protect the retina from ischemia-reperfusion injury.
The purpose of this study was to test the hypothesis that ischemia/reperfusion injury in the rat retina may be ameliorated by reducing retinal metabolism with either hypothermia or inhibitory GABA agonists. The intraocular pressure of each right eye in rats was raised to 130 mm Hg for 60 min with the left eye serving as normal control. The rats were divided into four groups in terms of drug and hypothermia treatment: (1) Untreated ischemia, (2) Hypothermia, (3) Baclofen/midazolam and (4) Baclofen/muscimol. Electroretinogram was recorded before ischemia and again after 10-day reperfusion. Histological analysis with H&E staining and cell counts was performed. Untreated ischemia/reperfusion resulted in severely reduced ERG responses. The ERG b-wave was reduced from 423+/-144 microV to 130+/-91 microV (mean+/-SD, n=5). With hypothermia the ERG b-wave was reduced from 499+/-80 microV to 237+/-111 microV (n=4). With combinations of baclofen and midazolam the ERG b-wave was reduced from 432+/-96 microV to 104+/-67 microV (n=7). In baclofen/muscimol treated eyes the ERG b-wave went from 426+/-101 microV to 148+/-118 microV (n=6). The histological tissue damage was severe in untreated ischemia and the baclofen/midazolam and baclofen/muscimol groups, but less severe in the hypothermia group. The GABA agonists do not provide any protection in our ischemia/reperfusion model. Our results are consistent with earlier reports that hypothermia may be helpful in ischemic conditions in the retina.
Traustason
Sindri
S
Department of Ophthalmology and Physiology, National University Hospital, University of Iceland, Reykjavík, Iceland.
Eysteinsson
Thor
T
Agnarsson
Bjarni A
BA
Stefánsson
Einar
E
D000818:Animals; D001418:Baclofen / Q000627:therapeutic use; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004596:Electroretinography / Q000187:drug effects; D005260:Female; D018755:GABA Agonists / Q000627:therapeutic use*; D018757:GABA Modulators / Q000627:therapeutic use; D007036:Hypothermia, Induced; D019194:Ischemic Preconditioning / Q000379:methods; D008874:Midazolam / Q000627:therapeutic use; D009118:Muscimol / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D012160:Retina / Q000378:metabolism / Q000503:physiopathology; D012171:Retinal Vessels / Q000187:drug effects* / Q000473:pathology
D004338:Drug Combinations; D018755:GABA Agonists; D018757:GABA Modulators; D009118:Muscimol; D001418:Baclofen; D008874:Midazolam