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Lateral gain is impaired in macular degeneration and can be targeted to restore vision in mice

Author

Listed:
  • M. Rizzi

    (UCL Inst. of Ophthalmology
    Centre for Cell and Gene Therapy, King’s College London)

  • K. Powell

    (UCL Inst. of Ophthalmology
    Centre for Cell and Gene Therapy, King’s College London)

  • M. R. Robinson

    (UCL Inst. of Ophthalmology)

  • T. Matsuki

    (UCL Inst. of Ophthalmology)

  • J. Hoke

    (UCL Inst. of Ophthalmology)

  • R. N. Maswood

    (UCL Inst. of Ophthalmology)

  • A. Georgiadis

    (UCL Inst. of Ophthalmology)

  • M. Georgiou

    (UCL Inst. of Ophthalmology)

  • P. R. Jones

    (UCL Inst. of Ophthalmology)

  • C. Ripamonti

    (CRS Ltd)

  • F. M. Nadal-Nicolás

    (Universidad de Murcia and IMIB-Arrixaca
    Retinal Neurophysiology Section, National Eye Institute, NIH)

  • M. Michaelides

    (UCL Inst. of Ophthalmology)

  • G. S. Rubin

    (UCL Inst. of Ophthalmology)

  • A. J. Smith

    (UCL Inst. of Ophthalmology
    Centre for Cell and Gene Therapy, King’s College London)

  • R. R. Ali

    (UCL Inst. of Ophthalmology
    Centre for Cell and Gene Therapy, King’s College London
    NIHR Biomedical Research Centre at Moorfields Eye Hospital and UCL Institute of Ophthalmology)

Abstract

Macular degeneration is a leading cause of blindness. Treatments to rescue vision are currently limited. Here, we study how loss of central vision affects lateral feedback to spared areas of the human retina. We identify a cone-driven gain control mechanism that reduces visual function beyond the atrophic area in macular degeneration. This finding provides an insight into the negative effects of geographic atrophy on vision. Therefore, we develop a strategy to restore this feedback mechanism, through activation of laterally projecting cells. This results in improved vision in Cnga3−/− mice, which lack cone function, as well as a mouse model of geographic atrophy. Our work shows that a loss of lateral gain control contributes to the vision deficit in macular degeneration. Furthermore, in mouse models we show that lateral feedback can be harnessed to improve vision following retinal degeneration.

Suggested Citation

  • M. Rizzi & K. Powell & M. R. Robinson & T. Matsuki & J. Hoke & R. N. Maswood & A. Georgiadis & M. Georgiou & P. R. Jones & C. Ripamonti & F. M. Nadal-Nicolás & M. Michaelides & G. S. Rubin & A. J. Smi, 2022. "Lateral gain is impaired in macular degeneration and can be targeted to restore vision in mice," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29666-x
    DOI: 10.1038/s41467-022-29666-x
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    References listed on IDEAS

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    1. Maximilian Joesch & Markus Meister, 2016. "A neuronal circuit for colour vision based on rod–cone opponency," Nature, Nature, vol. 532(7598), pages 236-239, April.
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