Retinal remodeling triggered by photoreceptor degenerations

Bryan W. Jones, Carl B. Watt, Jeanne M. Frederick, Wolfgang Baehr, Ching Kang Chen, Edward M. Levine, Ann H. Milam, Matthew M. Lavail, Robert E. Marc

Research output: Contribution to journalArticlepeer-review

397 Scopus citations

Abstract

Many photoreceptor degenerations initially affect rods, secondarily leading to cone death. It has long been assumed that the surviving neural retina is largely resistant to this sensory deafferentation. New evidence from fast retinal degenerations reveals that subtle plasticities in neuronal form and connectivity emerge early in disease. By screening mature natural, transgenic, and knockout retinal degeneration models with computational molecular phenotyping, we have found an extended late phase of negative remodeling that radically changes retinal structure. Three major transformations emerge: 1) Müller cell hypertrophy and elaboration of a distal glial seal between retina and the choroid/retinal pigmented epithelium; 2) apparent neuronal migration along glial surfaces to ectopic sites; and 3) rewiring through evolution of complex neurite fascicles, new synaptic foci in the remnant inner nuclear layer, and new connections throughout the retina. Although some neurons die, survivors express molecular signatures characteristic of normal bipolar, amacrine, and ganglion cells. Remodeling in human and rodent retinas is independent of the initial molecular targets of retinal degenerations, including defects in the retinal pigmented epithelium, rhodopsin, or downstream phototransduction elements. Although remodeling may constrain therapeutic intervals for molecular, cellular, or bionic rescue, it suggests that the neural retina may be more plastic than previously believed.

Original languageEnglish (US)
Pages (from-to)1-16
Number of pages16
JournalJournal of Comparative Neurology
Volume464
Issue number1
DOIs
StatePublished - Sep 8 2003
Externally publishedYes

Keywords

  • Animal models
  • Cell death
  • Molecular phenotyping
  • Plasticity
  • Remodeling
  • Retina
  • Retinitis pigmentosa

ASJC Scopus subject areas

  • General Neuroscience

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