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

Rizzi, M., Powell, K., Robinson, M. R. , Matsuki, T., Hoke, J., Maswood, R. N., Georgiadis, A., Georgiou, M., Jones, P. R. ORCID: 0000-0001-7672-8397, Ripamonti, C., Nadal-Nicolás, F. M., Michaelides, M., Rubin, G. S., Smith, A. J. & Ali, R. R. (2022). Lateral gain is impaired in macular degeneration and can be targeted to restore vision in mice. Nature Communications, 13(1), 2159. doi: 10.1038/s41467-022-29666-x


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.

Publication Type: Article
Additional Information: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit
Publisher Keywords: Animals; Geographic Atrophy; Macular Degeneration; Mice; Retinal Cone Photoreceptor Cells; Retinal Degeneration; Vision, Ocular
Subjects: R Medicine > RE Ophthalmology
Departments: School of Health & Psychological Sciences > Optometry & Visual Sciences
Text - Published Version
Available under License Creative Commons: Attribution International Public License 4.0.

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