Robust cone-mediated signaling persists late into rod photoreceptor degeneration.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Scalabrino, ML; Thapa, M; Chew, LA; Zhang, E; Xu, J; Sampath, AP; Chen, J; Field, GD

Published Date

  • August 30, 2022

Published In

Volume / Issue

  • 11 /

PubMed ID

  • 36040015

Pubmed Central ID

  • PMC9560159

Electronic International Standard Serial Number (EISSN)

  • 2050-084X

Digital Object Identifier (DOI)

  • 10.7554/eLife.80271

Language

  • eng

Conference Location

  • England