Visual Function is Gradually Restored During Retina Regeneration in Adult Zebrafish

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.

Different inflammation responses modulate Müller glia proliferation in the acute or chronically damaged zebrafish retina

“…Most vertebrates, including humans, cannot to regenerate retinal neurons that are lost due to traumatic injury or degenerative disease. In contrast, lower-order vertebrates, such as zebrafish, possess an extraordinary regenerative ability, which restores both the lost neurons and normal function to the damaged retina ( Iribarne, 2019 ; Hoang et al, 2020 ; Hammer et al, 2021 ). Upon neuronal loss in the zebrafish retina, Müller glia reprogram to a retinal progenitor cell-like state and re-enter the cell cycle to generate neuronal progenitor cells (NPCs).…”

Dynamic functional and structural remodeling during retinal regeneration in zebrafish

“…Our purpose was to gain insights into the process of functional recovery in correlation to histological regeneration and to identify any aberrant physiological responses. For example, is functional wiring recovered gradually over time (as shown for visually-mediated reflexes and behaviors following a light lesion ( Hammer et al, 2021 )) or does it re-appear suddenly at a certain time window? Does the overall shape of the waveform change over time?…”

The regeneration-responsive element careg monitors activation of Müller glia after MNU-induced damage of photoreceptors in the zebrafish retina

“…Despite the comparable structure, the loss of photoreceptor cells, rods, and cones, is irreversible in mammals, whereas they can be fully replaced in zebrafish ( Wan and Goldman, 2016 ; Angueyra and Kindt, 2018 ). In this species, the subsequent impairment to visual function is transient and progressively returns to the original level ( Hammer et al, 2021 ; Barrett et al, 2022 ). Beside the retina, other complex organs, such as fins, heart, spinal cord, and brain, can be fully restored in adult zebrafish ( Gemberling et al, 2013 ; Sehring et al, 2016 ; Mokalled and Poss, 2018 ; Marques et al, 2019 ).…”

“…As the topic of our study on MNU-mediated injury predominantly affects rods, UV-cones and the outer plexiform layer. Schematics of photoreceptor organization in a transversal section (A) and frontal flattened view (B), based on Raymond and Barthel (2004), Lagman et al (2015), and Noel et al (2021). INL, inner nuclear layer; rONL, rod outer nuclear layer; cONL, cone outer nuclear layer; OPL, outer plexiform layer; RPE, retinal pigmented epithelium; DC, double cones (red/green spectral sensitivity); LC, long single cones (blue spectral sensitivity); SC, short single cone (UV spectral sensitivity).…”