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

Nat Commun. 2022 Apr 20;13(1):2159. doi: 10.1038/s41467-022-29666-x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Geographic Atrophy* / genetics
  • Geographic Atrophy* / therapy
  • Macular Degeneration* / genetics
  • Mice
  • Retinal Cone Photoreceptor Cells / physiology
  • Retinal Degeneration* / complications
  • Retinal Degeneration* / genetics
  • Retinal Degeneration* / therapy
  • Vision, Ocular