Unilateral corneal insult in Zebrafish results in a bilateral cell shape and identity modification, supporting wound closure

2021 ◽  
Author(s):  
Kaisa Ikkala ◽  
Vassilis Stratoulias ◽  
Frederic Michon

AbstractMost of terrestrial and aquatic vertebrates are equipped with camera-type eyes, offering a focused and clear sight. This apparatus is rendered inefficient if its most superficial and transparent element, the cornea, is opaque. This structure, prone to environmental aggressions, bears excellent wound healing capabilities to preserve vision. Up to date, most of the corneal wound healing studies are made on mammals. Here, for the first time, zebrafish is used as model to study wound closure of corneal epithelium after abrasion. Our study demonstrates a swift wound closure after corneal insult. Interestingly, a unilateral wound induces a bilateral response. While cell proliferation is increased during wound closure, this parameter is not crucial, and cell rearrangements seems to be the driving force. Furthermore, we discovered a profound change in epithelial cell transcriptomic signature after abrasion, reflecting a modulation of cell identity and increase of phenotypic plasticity. The latter seems to unlock terminally differentiated cell capacities for wound healing, which could be the key for a speed up organ regeneration. Our results prove that zebrafish cornea is a powerful model to investigate, not only corneal wound healing, but ectodermal organ pathophysiology.

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Kaisa Ikkala ◽  
Vassilis Stratoulias ◽  
Frederic Michon

AbstractThe cornea, transparent and outermost structure of camera-type eyes, is prone to environmental challenges, but has remarkable wound healing capabilities which enables to preserve vision. The manner in which cell plasticity impacts wound healing remains to be determined. In this study, we report rapid wound closure after zebrafish corneal epithelium abrasion. Furthermore, by investigating the cellular and molecular events taking place during corneal epithelial closure, we show the induction of a bilateral response to a unilateral wound. Our transcriptomic results, together with our TGF-beta receptor inhibition experiments, demonstrate conclusively the crucial role of TGF-beta signaling in corneal wound healing. Finally, our results on Pax6 expression and bilateral wound healing, demonstrate the decisive impact of epithelial cell plasticity on the pace of healing. Altogether, our study describes terminally differentiated cell competencies in the healing of an injured cornea. These findings will enhance the translation of research on cell plasticity to organ regeneration.


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