Retinal Neuroprotection against Ischemia-Reperfusion Damage Induced by Postconditioning

• Published in: Investigative ophthalmology & visual science 2009-08, Vol.50 (8), p.3922-3930
• Main Authors: Fernandez, Diego C, Bordone, Melina P, Chianelli, Monica S, Rosenstein, Ruth E
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cardiology. Vascular system; Cell Survival; Cycloheximide - pharmacology; Cytoprotection; Disease Models, Animal; Electroretinography; Eye and associated structures. Visual pathways and centers. Vision; Fluorescent Antibody Technique, Indirect; Fundamental and applied biological sciences. Psychology; Glial Fibrillary Acidic Protein - metabolism; Intraocular Pressure; Male; Medical sciences; Ocular Hypertension - complications; Ophthalmology; Protein Synthesis Inhibitors - pharmacology; Rats; Rats, Wistar; Reperfusion - methods; Reperfusion Injury - etiology; Reperfusion Injury - physiopathology; Reperfusion Injury - prevention & control; Retina - drug effects; Retina - physiology; Retinal Diseases - etiology; Retinal Diseases - physiopathology; Retinal Diseases - prevention & control; Synaptophysin - metabolism; Vertebrates: nervous system and sense organs; Vimentin - metabolism
• ISSN: 0146-0404; 1552-5783; 1552-5783
• DOI: 10.1167/iovs.08-3344

Retinal ischemia may provoke blindness. There is no effective treatment against retinal ischemic damage. The authors investigated whether brief intermittent ischemia applied during the onset of reperfusion (i.e., postconditioning) protects the retina from ischemia-reperfusion damage. Ischemia was induced by increasing intraocular pressure (120 mm Hg for 40 or 60 minutes). Five minutes after reperfusion, animals underwent 3, 7, or 10 cycles of 1-minute ischemia/1-minute reperfusion or 7 minutes of ischemia. In other experiments, seven ischemia-reperfusion cycles were applied 10, 30, and 60 minutes or 24 hours after ischemia. A group of animals received intraperitoneal injections of cycloheximide (CHX) 1 minute before or 6 hours after postconditioning. Seven or 14 days after ischemia, animals were subjected to electroretinography and histologic analysis. Seven ischemia-reperfusion cycles applied 5 minutes after reperfusion afforded significant functional protection in eyes exposed to ischemia-reperfusion injury. A marked reduction in retinal thickness and an increase in Müller cell glial fibrillary acidic protein (GFAP) levels were observed in ischemic retinas, whereas postconditioning preserved retinal structure and reduced GFAP levels in Müller cells. Postconditioning initiated between 5 and 60 minutes after reperfusion protected against ischemic injury. Retinal protection depended on the number of ischemia-reperfusion cycles. One 7-minute pulse applied 5 minutes after ischemia induced significant protection against ischemic damage. Retinal protection induced by postconditioning was reversed by CHX (injected 1 minute before but not 6 hours after postconditioning). These results indicate that postconditioning significantly protected retinal function and histology from ischemia-reperfusion injury through a mechanism that involved de novo synthesis of protein.