title: Delayed post-ischemic conditioning significantly improves the outcome after retinal ischemia.
abstract: In previous studies, it was shown that post-conditioning, a transient period of brief ischemia following prolonged severe ischemia in the retina, could provide significant improvement in post-ischemic recovery, attenuation of cell loss, and decreased apoptosis. These studies showed that post-conditioning effectively prevented damage after retinal ischemia when it was instituted early (within 1 h) in the post-ischemic period. While post-ischemic conditioning holds high promise of clinical translation, patients often present late after the onset of retinal ischemia and therefore immediate application of this anti-ischemic maneuver is generally not feasible. In this study, we examined the hypothesis that application of a post-conditioning stimulus at 24 h or greater following the end of prolonged ischemia would decrease the extent of ischemic injury. Ischemia was induced in rat retina in vivo. Recovery after ischemia followed by 5 min of post-conditioning brief ischemia 24 or 48 h after prolonged ischemia was assessed functionally (electroretinography) and histologically at 7 days after ischemia and post-conditioning or sham post-conditioning. We found that the brief ischemic stimulus applied 24, but not 48 h after prolonged ischemia significantly improved functional recovery and decreased histological damage induced by prolonged ischemia. We conclude that within a defined time window, delayed post-ischemic conditioning ameliorated post-ischemic injury in rats. Compared to earlier studies, the present work demonstrates for the first time the novel ability of a significantly delayed ischemic stimulus to provide robust neuroprotection in the retina following ischemia.
authors.affiliation: Department of Anesthesia and Critical Care, The University of Chicago, IL, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Dreixler
authors.forename: Jacqueline N
authors.initials: JN
authors.lastname: Poston
authors.forename: Afzhal R
authors.initials: AR
authors.lastname: Shaikh
authors.forename: Michael
authors.initials: M
authors.lastname: Alexander
authors.forename: Kelsey Y
authors.initials: KY
authors.lastname: Tupper
authors.forename: Marcus M
authors.initials: MM
authors.lastname: Marcet
authors.forename: Myriam
authors.initials: M
authors.lastname: Bernaudin
authors.forename: Steven
authors.initials: S
authors.lastname: Roth
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D002452:Cell Count; D019610:Cytoprotection; D004596:Electroretinography; D007429:Intraocular Pressure / Q000502:physiology; D057775:Ischemic Postconditioning; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D012164:Retinal Diseases / Q000503:physiopathology / Q000517:prevention & control*; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000502:physiology; D012171:Retinal Vessels / Q000502:physiology*; D014065:Tonometry, Ocular