Abstract
In comparison to mammals, zebrafish are able to regenerate many organs and tissues, including the central nervous system (CNS). Within the CNS-derived neural retina, light lesions result in a loss of photoreceptors and the subsequent activation of Müller glia, the retinal stem cells. Müller glia-derived progenitors differentiate and eventually restore the anatomical tissue architecture within 4 weeks. However, little is known about how light lesions impair vision functionally, as well as how and to what extent visual function is restored during the course of regeneration, in particular in adult animals. Here, we applied quantitative behavioral assays to assess restoration of visual function during homeostasis and regeneration in adult zebrafish. We developed a novel vision-dependent social preference test, and show that vision is massively impaired early after lesion, but is restored to pre-lesion levels within 7 days after lesion. Furthermore, we employed a quantitative optokinetic response assay with different degrees of difficulty, similar to vision tests in humans. We found that vision for easy conditions with high contrast and low level of detail, as well as color vision, was restored around 7–10 days post lesion. Vision under more demanding conditions, with low contrast and high level of detail, was regained only later from 14 days post lesion onwards. Taken together, we conclude that vision based on contrast sensitivity, spatial resolution and the perception of colors is restored after light lesion in adult zebrafish in a gradual manner.
Highlights
Vision is one of the most important senses in all vertebrate species, in humans
Infrared illumination was provided from the bottom and an infrared-sensitive camera centered above the arena was used to record the movement of a single test fish
Our results show that dark-light preference reveals significant differences under light and dark conditions in unlesioned fish but that individual variability impedes assessment of functional recovery after light lesion
Summary
Vision is one of the most important senses in all vertebrate species, in humans. Various attempts have been made to prevent or restore vision loss using prosthetic devices, gene therapy, optogenetics as well as cell transplantations (Salman et al, 2021). In a N-methyl-N-nitrosourea-induced retinal degeneration model it was shown that the optokinetic response, a reflexive and stereotypic eye movement, is restored within 15 days after lesion (Maurer et al, 2014). Taken together, these studies indicate that the kinetic of vision recovery can be addressed functionally in the course of regeneration and is strongly dependent on the applied lesion model. The systematic application of behavioral assays to assess the degree of functional recovery is currently still largely missing in zebrafish
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