Homeostatic plasticity in the retina is associated with maintenance of night vision during retinal degenerative disease
Abstract
Neuronal plasticity of the inner retina has been observed in response to photoreceptor degeneration. Typically, this phenomenon has been considered maladaptive and may preclude vision restoration in the blind. However, several recent studies utilizing triggered photoreceptor ablation have shown adaptive responses in bipolar cells expected to support normal vision. Whether such homeostatic plasticity occurs during progressive photoreceptor degenerative disease to help maintain normal visual behavior is unknown. We addressed this issue in an established mouse model of Retinitis Pigmentosa caused by the P23H mutation in rhodopsin. We show robust modulation of the retinal transcriptomic network, reminiscent of the neurodevelopmental state, and potentiation of rod – rod bipolar cell signaling following rod photoreceptor degeneration. Additionally, we found highly sensitive night vision in P23H mice even when more than half of the rod photoreceptors were lost. These results suggest retinal adaptation leading to persistent visual function during photoreceptor degenerative disease.
Data availability
Sequencing data have been uploaded in GEO, accession numbers: GSE152474 (1-month-old samples) and GSE156533 (3-month-old samples).
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Transcriptomic profiling in juvenile P23H Retinitis Pigmentosa mouse retinasNCBI Gene Expression Omnibus, GSE152474.
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Transcriptomic profiling in 3-month-old P23H Retinitis Pigmentosa mouse retinasNCBI Gene Expression Omnibus, GSE156533.
Article and author information
Author details
Funding
National Eye Institute (R00 EY026651)
- Frans Vinberg
Research to Prevent Blindness (Unrestricted grant to the Department of Ophthalmology and Visual Sciences,University of Utah)
- Frans Vinberg
International Retinal Research Foundation (Regular Grant)
- Frans Vinberg
Research to Prevent Blindness (Dr. H. James and Carole Free Career Development)
- Frans Vinberg
National Eye Institute (R01 EY009339)
- Krzysztof Palczewski
National Eye Institute (R24 EY027283)
- Krzysztof Palczewski
Eye and Tissue Bank Foundation (Postdoctoral Award)
- Henri Leinonen
Finnish Cultural Foundation (Postdoctoral Award)
- Henri Leinonen
Orion Research Foundation (Postdoctoral Award)
- Henri Leinonen
Research to Prevent Blindness (Unrestricted grant to the Department of Ophthalmology,University of California,Irvine)
- Krzysztof Palczewski
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Lois Smith, Boston Children's Hospital/Harvard Medical School, United States
Ethics
Animal experimentation: All experimental protocols adhered to Guide for the Care and Use of Laboratory Animals and were approved by the institutional Animal Studies Committees at the University of Utah (protocol #20-17015) and University of California, Irvine (protocol #AUP-18-124).
Version history
- Received: May 28, 2020
- Accepted: September 8, 2020
- Accepted Manuscript published: September 22, 2020 (version 1)
- Version of Record published: October 1, 2020 (version 2)
Copyright
© 2020, Leinonen et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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