Robert E. Marc is a principal of Signature Immunologics Inc., manufacturer of the anti-hapten IgGs used in this research.
Retinal remodeling triggered by photoreceptor degenerations
Article first published online: 10 JUL 2003
Copyright © 2003 Wiley-Liss, Inc.
Journal of Comparative Neurology
Volume 464, Issue 1, pages 1–16, 8 September 2003
How to Cite
Jones, B. W., Watt, C. B., Frederick, J. M., Baehr, W., Chen, C.-K., Levine, E. M., Milam, A. H., Lavail, M. M. and Marc, R. E. (2003), Retinal remodeling triggered by photoreceptor degenerations. J. Comp. Neurol., 464: 1–16. doi: 10.1002/cne.10703
- Issue published online: 10 JUL 2003
- Article first published online: 10 JUL 2003
- Manuscript Revised: 27 MAR 2003
- Manuscript Received: 10 JAN 2003
- National Eye Institute. Grant Numbers: EY01919, EY02162, EY06842, EY08123, EY02576
- Research to Prevent Blindness
- Foundation Fighting Blindness
- Macula Vision Research Foundation
- retinitis pigmentosa;
- animal models;
- molecular phenotyping;
- cell death;
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. J. Comp. Neurol. 464:1–16, 2003. © 2003 Wiley-Liss, Inc.