Reentrant spiral waves of spreading depression cause macular degeneration in hypoglycemic chicken retina

Yufei Yu, Laura M. Santos, Linda A. Mattiace, Manoel L. Costa, Luciano C. Ferreira, Kelly Benabou, Ana H. Kim, John Abrahams, Michael V.L. Bennett, Renato Rozental

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Spreading depression (SD), a slow diffusion-mediated self-sustained wave of depolarization that severely disrupts neuronal function, has been implicated as a cause of cellular injury in a number of central nervous system pathologies, including blind spots in the retina. Here we show that in the hypoglycemic chicken retina, spontaneous episodes of SD can occur, resulting in irreversible punctate lesions in the macula, the region of highest visual acuity in the central region of the retina. These lesions in turn can act as sites of origin for secondary self-sustained reentrant spiral waves of SD that progressively enlarge the lesions. Furthermore, we show that the degeneration of the macula under hypoglycemic conditions can be prevented by blocking reentrant spiral SDs or by blocking caspases. The observation that spontaneous formation of reentrant spiral SD waves leads to the development of progressive retinal lesions under conditions of hypoglycemia establishes a potential role of SD in initiation and progression of macular degeneration, one of the leading causes of visual disability worldwide.

Original languageEnglish (US)
Pages (from-to)2585-2589
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number7
DOIs
StatePublished - Feb 14 2012

Keywords

  • Diabetes
  • Retinal migraine
  • Scotomas

ASJC Scopus subject areas

  • General

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