Restoration of cone circuit functionality in the regenerating adult zebrafish retina

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 lesion. To assess functional recovery of
cones and downstream outer retinal circuits, we exploited colour
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- versus On-responses and find 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.