Retinal remodeling triggered by photoreceptor degenerations.

Jones BW, Watt CB, Frederick JM, Baehr W, Chen CK, Levine EM, Milam AH, Lavail MM, Marc RE
J Comp Neurol. 2003 464 (1): 1-16

PMID: 12866125 · DOI:10.1002/cne.10703

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.

Copyright 2003 Wiley-Liss, Inc.

MeSH Terms (28)

Aging Amino Acids Animals Animals, Genetically Modified Cell Death Cell Movement Disease Models, Animal gamma-Aminobutyric Acid Glutathione Humans Image Processing, Computer-Assisted Immunohistochemistry Indoles Mice Mice, Knockout Microscopy, Electron Mutation Neuroglia Neurons Phenotype Photoreceptor Cells Pigment Epithelium of Eye Rats Retinal Degeneration Rhodopsin Synapses Taurine Tolonium Chloride

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