Involvement of glutamate in retinal protection against ischemia/reperfusion damage induced by post-conditioning.
Retinal ischemia could provoke blindness and there is no effective treatment against retinal ischemic damage. Brief intermittent ischemia applied during the onset of reperfusion (i.e., post-conditioning) protects the retina from ischemia/reperfusion injury. Multiple evidences support that glutamate is implicated in retinal ischemic damage. We investigated the involvement of glutamate clearance in post-conditioning-induced protection. For this purpose, ischemia was induced by increasing intra-ocular pressure for 40 min, and 5 min after reperfusion, animals underwent seven cycles of 1 min/1 min ischemia/reperfusion. One, three, or seven days after ischemia, animals were subjected to electroretinography and histological analysis. The functional and histological protection induced by post-conditioning was evident at 7 (but not 1 or 3) days post-ischemia. An increase in Müller cell glial fibrillary acidic protein (GFAP) levels was observed at 1, 3, and 7 days after ischemia, whereas post-conditioning reduced GFAP levels of Müller cells at 3 and 7 days post-ischemia. Three days after ischemia, a significant decrease in glutamate uptake and glutamine synthetase activity was observed, whereas post-conditioning reversed the effect of ischemia. The intravitreal injection of supraphysiological levels of glutamate mimicked electroretinographic and histological alterations provoked by ischemia, which were abrogated by post-conditioning. These results support the involvement of glutamate in retinal protection against ischemia/reperfusion damage induced by post-conditioning.
Fernandez
Diego C
DC
Department of Human Biochemistry, Laboratory of Retinal Neurochemistry and Experimental Ophthalmology, School of Medicine, University of Buenos Aires/CEFyBO, CONICET, Buenos Aires, Argentina.
Chianelli
Mónica S
MS
Rosenstein
Ruth E
RE
D000818:Animals; D004596:Electroretinography; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D018698:Glutamic Acid / Q000493:pharmacokinetics*; D005972:Glutaminase / Q000378:metabolism; D005973:Glutamine / Q000493:pharmacokinetics; D007429:Intraocular Pressure; D019194:Ischemic Preconditioning; D008297:Male; D018696:Neuroprotective Agents / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D012160:Retina / Q000473:pathology* / Q000502:physiology; D014316:Tritium
D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents; D005973:Glutamine; D014316:Tritium; D018698:Glutamic Acid; D005972:Glutaminase; D005974:Glutamate-Ammonia Ligase