Unilateral zebrafish corneal injury induces bilateral cell plasticity supporting wound closure

Abstract

The 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.

Zebrafish cornea formation and homeostasis reflect robustness in camera-type eye biology, regardless of its environment

“…10). We confirmed the results obtained previously (Ikkala et al, 2022), namely the loss of Pax6a expression in central cornea during the wound healing period. The krtt1c19e expression exhibited an interesting dynamics.…”

“…The loss of one pax6 allele, such as seen in the context of the rare disease called aniridia, as well as Pax6 overexpression showed overlapping effects, such as reduced krt12 expression, reduced adult corneal diameter or thickness, and altered wound healing (Ramaesh et al, 2003;Dora et al, 2008). Thus, an appropriate level of Pax6 is necessary to maintain corneal integrity, as we presented previously (Ikkala et al, 2022).…”

“…2). Previously, we noticed a clear distinction between central and peripheral cell surface appearance in adult zebrafish (Ikkala et al, 2022). In the periphery, the apical cell area was remarkably smaller and the microridges more abundant compared to the central cornea.…”

Zebrafish cornea formation and homeostasis reveal a slow maturation process, similarly to terrestrial vertebrates’ corneas

“…The loss of one Pax6 allele, such as seen in the context of the rare disease called aniridia, characterized by an hypoplasia or lack of iris, as well as Pax6 overexpression, showed overlapping effects such as reduced krt12 expression, reduced adult corneal diameter or thickness, and altered wound healing (Ramaesh et al, 2003;Dora et al, 2008). Thus, an appropriate level of Pax6 is necessary to maintain corneal integrity, as we have previously demonstrated in zebrafish cornea (Ikkala et al, 2022b).…”

“…Pax6a expression was suppressed during the wound healing process (Ikkala et al, 2022b). Therefore, here we followed the expression of these two markers during wound healing to investigate a possible reset of corneal maturation during that process.…”