Restoration of cone-circuit functionality in the regenerating adult zebrafish retina

Evelyn Abraham, Hella Hartmann, Takeshi Yoshimatsu, Tom Baden, Michael Brand

Research output: Contribution to journalArticlepeer-review

Abstract

Unlike humans, teleosts like zebrafish exhibit robust retinal regeneration after injury from endogenous stem cells. However, it is unclear if regenerating cone photoreceptors regain physiological function and integrate correctly into post-synaptic circuits. We used two-photon calcium imaging of living adult retina to examine photoreceptor responses before and after light-induced lesions. To assess functional recovery of cones and downstream outer retinal circuits, we exploited color opponency; UV cones exhibit intrinsic Off-response to blue light, but On-response to green light, which depends on feedback signals from outer retinal circuits. Accordingly, we assessed the presence and quality of Off- vs. On-responses and found that regenerated UV cones regain both Off-responses to short-wavelength and On-responses to long-wavelength light within 3 months after lesion. Therefore, physiological circuit functionality is restored in regenerated cone photoreceptors, suggesting that inducing endogenous regeneration is a promising strategy for human retinal repair.

Original languageEnglish
Pages (from-to)2158-2170.e6
JournalDevelopmental cell
Volume59
Issue number16
DOIs
StatePublished - Aug 19 2024

Keywords

  • blindness
  • Ca imaging
  • CNS
  • functional restoration
  • photoreceptors
  • physiological recovery
  • regeneration
  • retina
  • UV cones
  • zebrafish

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