Retinal remodeling triggered by photoreceptor degenerations
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.
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Rodents with genetic mutations leading to an RP-like form of blindness show significant remodelling of the retinal circuits after photoreceptor degeneration.
“These rodents show a significant remodelling of the retinal circuits after photoreceptor degeneration [207].”
From Advances in visual prostheses: engineering and biological challenges (2022) · cites this paper as [207]
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- Authors
- Jones, B. W., Watt, C. B., Frederick, J. M., Baehr, W., Chen, C., Levine, E. M., Milam, A. H., Lavail, M. M., & Marc, R. E.
- Affiliations
- University of Utah (US)
- University of Pennsylvania (US)
- University of California, San Francisco (US)
- Corresponding author
- Jones, Bryan W.
- ORCID
- Venue
- Journal of Comparative Neurology
- Publisher
- Wiley
- Published
- 2003-07-10
- Volume
- 464
- Issue
- 1
- Pages
- 1-16
- ISSN
- 0021-9967 (ISSN-L)
- 1096-9861
- OpenAlex
- W2069903330
- Cited by
- 476
- References
- 60
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 15 · 2023: 20 · 2022: 21 · 2021: 18 · 2020: 17 · 2019: 16 · 2018: 11 · 2017: 20 · 2016: 22 · 2015: 24 · 2014: 23 · 2013: 30 · 2012: 33
- FWCI
- 7.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Comparative Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ey013760-15)
- National Eye Institute (R01-EY013760, EY-06842, EY02162, P30EY002162, EY02576, EY-01919, R01EY008123, EY 08123, R01EY002576)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
- Keywords
- retinal degeneration, retinal remodeling, photoreceptor degeneration, cone photoreceptors, deafferentation, neuronal migration, neurite fasciculation, synaptic remodeling, inner nuclear layer, retinal plasticity, retinal pigment epithelium, rhodopsin, phototransduction, bipolar cells, amacrine cells, retinal ganglion cells, retinal degeneration models
- MeSH terms
- Aging, Amino Acids, Animals, Cell Movement, Disease Models, Animal, gamma-Aminobutyric Acid, Glutathione, Humans, Image Processing, Computer-Assisted, Immunohistochemistry, Indoles, Microscopy, Electron, Mutation, Neuroglia, Neurons, Phenotype, Photoreceptor Cells, Pigment Epithelium of Eye, Retinal Degeneration, Rhodopsin, Synapses, Taurine, Tolonium Chloride, Cell Death, Mice, Knockout, Animals, Genetically Modified, Mice, Rats
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