Retinal remodeling in inherited photoreceptor degenerations.
Photoreceptor degenerations initiated in rods or the retinal pigmented epithelium usually evoke secondary cone death and sensory deafferentation of the surviving neural retina. In the mature central nervous system, deafferentation evokes atrophy and connective re-patterning. It has been assumed that the neural retina does not remodel, and that it is a passive survivor. Screening of advanced stages of human and rodent retinal degenerations with computational molecular phenotyping has exposed a prolonged period of aggressive negative remodeling in which neurons migrate along aberrant glial columns and seals, restructuring the adult neural retina (1). Many neurons die, but survivors rewire the remnant inner plexiform layer (IPL), forming thousands of novel ectopic microneuromas in the remnant inner nuclear layer (INL). Bipolar and amacrine cells engage in new circuits that are most likely corruptive. Remodeling in human and rodent retinas emerges regardless of the molecular defects that initially trigger retinal degenerations. Although remodeling may constrain therapeutic intervals for molecular, cellular, or bionic rescue, the exposure of intrinsic retinal remodeling by the removal of sensory control in retinal degenerations suggests that neuronal organization in the normal retina may be more plastic than previously believed.
John A. Moran Eye Center, University of Utah School of Medicine, Salt Lake City, UT 84132, USA. robert.marc@hsc.utah.edu
Robert E
RE
Marc
Bryan W
BW
Jones
D025042:Amacrine Cells / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D000818:Animals; D030801:Animals, Genetically Modified; D015415:Biomarkers; D016923:Cell Death / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D002828:Choristoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009416:Nerve Regeneration / Q000235:genetics*; D009434:Neural Pathways / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009463:Neuroma / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000235:genetics*; D010641:Phenotype; D010786:Photoreceptor Cells / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D017729:Presynaptic Terminals / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D051381:Rats; D012162:Retinal Degeneration / Q000150:complications / Q000235:genetics* / Q000473:pathology*
D015415:Biomarkers