Ischemia-induced spreading depolarization in the retina

Anja I. Srienc, Kyle R. Biesecker, Angela M. Shimoda, Joanna Kur, Eric A. Newman

Research output: Contribution to journalArticle

3 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1579-1591
Number of pages13
JournalJournal of Cerebral Blood Flow and Metabolism
Volume36
Issue number9
DOIs
StatePublished - Sep 1 2016

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Keywords

  • Branch retinal vein occlusion
  • NMDA antagonist
  • hypoxia
  • retinal ischemia
  • spreading depolarization

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