1. Neuroscience

Robust cone-mediated signaling persists late into rod photoreceptor degeneration

  1. Miranda L Scalabrino
  2. Mishek Thapa
  3. Lindsey A Chew
  4. Esther Zhang
  5. Jason Xu
  6. Alapakkam P Sampath
  7. Jeannie Chen
  8. Greg D Field  Is a corresponding author
  1. Duke University, United States
  2. University of California, Los Angeles, United States
  3. University of Southern California, United States
https://doi.org/10.7554/eLife.80271
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Cite this article
  1. Miranda L Scalabrino
  2. Mishek Thapa
  3. Lindsey A Chew
  4. Esther Zhang
  5. Jason Xu
  6. Alapakkam P Sampath
  7. Jeannie Chen
  8. Greg D Field
(2022)
Robust cone-mediated signaling persists late into rod photoreceptor degeneration
eLife 11:e80271.
https://doi.org/10.7554/eLife.80271
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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

  1. Miranda L Scalabrino

    Department of Neurobiology, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Mishek Thapa

    Department of Neurobiology, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2868-7348

  3. Lindsey A Chew

    Department of Neurobiology, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2040-1579

  4. Esther Zhang

    Department of Neurobiology, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Jason Xu

    Department of Statistical Science, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5472-3720

  6. Alapakkam P Sampath

    Jules Stein Eye Institute, Department of Ophthalmology, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Jeannie Chen

    Zilkha Neurogenetics Institute, University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7904-9629

  8. Greg D Field

    Department of Neurobiology, Duke University, Durham, United States
    For correspondence
    field@neuro.duke.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5942-2679

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.

Reviewing Editor

  1. Marla B Feller, University of California, Berkeley, United States

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.

Version history

  1. Preprint posted: April 28, 2022 (view preprint)
  2. Received: May 13, 2022
  3. Accepted: August 25, 2022
  4. Accepted Manuscript published: August 30, 2022 (version 1)
  5. Version of Record published: October 13, 2022 (version 2)
  6. Version of Record updated: January 12, 2023 (version 3)

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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  1. Miranda L Scalabrino
  2. Mishek Thapa
  3. Lindsey A Chew
  4. Esther Zhang
  5. Jason Xu
  6. Alapakkam P Sampath
  7. Jeannie Chen
  8. Greg D Field
(2022)
Robust cone-mediated signaling persists late into rod photoreceptor degeneration
eLife 11:e80271.
https://doi.org/10.7554/eLife.80271

Share this article

https://doi.org/10.7554/eLife.80271

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