Involvement of glutamate in retinal protection against ischemia/reperfusion damage induced by post-conditioning

• Published in: Journal of neurochemistry 2009-10, Vol.111 (2), p.488-498
• Main Authors: Fernandez, Diego C, Chianelli, Mónica S, Rosenstein, Ruth E
• Format: Article
• Language: English
• Subjects: Animals; Biochemistry; Biological and medical sciences; Cardiology. Vascular system; Cellular biology; Electroretinography; Glial Fibrillary Acidic Protein - metabolism; glutamate; Glutamate-Ammonia Ligase - metabolism; Glutamic Acid - pharmacokinetics; Glutaminase - metabolism; glutamine; Glutamine - pharmacokinetics; Histology; Intraocular Pressure; Ischemia; Ischemic Preconditioning; Male; Medical sciences; Neurology; Neuroprotective Agents - pharmacokinetics; Ophthalmology; post-conditioning; Rats; Rats, Wistar; Reperfusion Injury - metabolism; Reperfusion Injury - pathology; Reperfusion Injury - prevention & control; Retina; Retina - pathology; Retina - physiology; Tritium; Vision disorders
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2009.06334.x

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.