title: Ischemia-induced spreading depolarization in the retina.
abstract: Cortical spreading depolarization is a metabolically costly phenomenon that affects the brain in both health and disease. Following severe stroke, subarachnoid hemorrhage, or traumatic brain injury, cortical spreading depolarization exacerbates tissue damage and enlarges infarct volumes. It is not known, however, whether spreading depolarization also occurs in the retina in vivo. We report now that spreading depolarization episodes are generated in the in vivo rat retina following retinal vessel occlusion produced by photothrombosis. The properties of retinal spreading depolarization are similar to those of cortical spreading depolarization. Retinal spreading depolarization waves propagate at a velocity of 3.0 ± 0.1 mm/min and are associated with a negative shift in direct current potential, a transient cessation of neuronal spiking, arteriole constriction, and a decrease in tissue O2 tension. The frequency of retinal spreading depolarization generation in vivo is reduced by administration of the NMDA antagonist MK-801 and the 5-HT(1D) agonist sumatriptan. Branch retinal vein occlusion is a leading cause of vision loss from vascular disease. Our results suggest that retinal spreading depolarization could contribute to retinal damage in acute retinal ischemia and demonstrate that pharmacological agents can reduce retinal spreading depolarization frequency after retinal vessel occlusion. Blocking retinal spreading depolarization generation may represent a therapeutic strategy for preserving vision in branch retinal vein occlusion patients.
authors.affiliation: Graduate Program in Neuroscience, University of Minnesota, MN, USA Medical Scientist Training Program, University of Minnesota, MN, USA.
authors.forename: Anja I
authors.initials: AI
authors.lastname: Srienc
authors.affiliation: Graduate Program in Neuroscience, University of Minnesota, MN, USA.
authors.forename: Kyle R
authors.initials: KR
authors.lastname: Biesecker
authors.affiliation: Department of Neuroscience, University of Minnesota, MN, USA.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Shimoda
authors.affiliation: Department of Neuroscience, University of Minnesota, MN, USA.
authors.forename: Joanna
authors.initials: J
authors.lastname: Kur
authors.affiliation: Department of Neuroscience, University of Minnesota, MN, USA ean@umn.edu.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Newman
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology*; D013181:Cortical Spreading Depression; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000627:therapeutic use; D018691:Excitatory Amino Acid Antagonists; D051381:Rats; D012160:Retina / Q000293:injuries / Q000503:physiopathology*; D015356:Retinal Artery Occlusion / Q000188:drug therapy; D058825:Serotonin 5-HT1 Receptor Agonists; D018170:Sumatriptan / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D018691:Excitatory Amino Acid Antagonists; D058825:Serotonin 5-HT1 Receptor Agonists; D016291:Dizocilpine Maleate; D018170:Sumatriptan
keywords: Branch retinal vein occlusion; NMDA antagonist; hypoxia; retinal ischemia; spreading depolarization