Robust cone-mediated signaling persists late into rod photoreceptor degeneration
- Duke University, United States
- University of California, Los Angeles, United States
- University of Southern California, United States
Abstract
Rod photoreceptor degeneration causes deterioration in the morphology and physiology of cone photoreceptors along with changes in retinal circuits. These changes could diminish visual signaling at cone-mediated light levels, thereby limiting the efficacy of treatments such as gene therapy for rescuing normal, cone-mediated vision. However, the impact of progressive rod death on cone-mediated signaling remains unclear. To investigate the fidelity of retinal ganglion cell (RGC) signaling throughout disease progression, we used a mouse model of rod degeneration (Cngb1neo/neo). Despite clear deterioration of cone morphology with rod death, cone-mediated signaling among RGCs remained surprisingly robust: spatiotemporal receptive fields changed little and the mutual information between stimuli and spiking responses was relatively constant. This relative stability held until nearly all rods had died and cones had completely lost well-formed outer segments. Interestingly, RGC information rates were higher and more stable for natural movies than checkerboard noise as degeneration progressed. The main change in RGC responses with photoreceptor degeneration was a decrease in response gain. These results suggest that gene therapies for rod degenerative diseases are likely to prolong cone-mediated vision even if there are changes to cone morphology and density.
Data availability
Data to generate all summary plots in Figures 1-11 are included in the following GitHub repository: https://github.com/mishek-thapa/cng-data; they are also available as source data files with the manuscript. For physiology data, we have not provided the raw data files (voltage as a function of time on all electrodes) because these files are enormous (in excess of 5 TB). Raw data will be provided upon request by contacting the corresponding author. Requests will be met provided the data will not be used for commercial purposes. MATLAB code for information calculations are available in the above GitHub repository. The Cngbneo/neo mouse model is available to be shared upon request. Raw image files from Figure 1 can be found at doi:10.5061/dryad.x95x69pmq.
Article and author information
Author details
Funding
National Eye Institute (EY024280)
- Alapakkam P Sampath
- Jeannie Chen
- Greg D Field
National Eye Institute (EY5722)
- Greg D Field
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Mice were used according to Duke University Institutional Animal Care and Use Committee guidelines (protocol A084-21-04) and the Association for Research in Vision and Ophthalmology guidelines for the use of animals in vision research.
Copyright
© 2022, Scalabrino 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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Robust cone-mediated signaling persists late into rod photoreceptor degeneration
eLife 11:e80271.
https://doi.org/10.7554/eLife.80271
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