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

Abstract

Most 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.

Inherited mitochondrial dysfunction triggered by OPA1 mutation impacts the sensory innervation fibre identity, functionality and regenerative potential in the cornea

“…The epithelial wound closure was monitored everyday using fluorescein staining to measure the surface of the epithelial area still unclosed (Fig.7A). Similarly to our previous work have shown 44,45 , the corneal epithelium wound was closed 3 days after abrasion. Moreover, we did not observe a difference in the epithelial closure time upon OPA1 mutation.…”

“…7A). Similarly to our previous work have shown 44,45 , the corneal epithelium wound was closed 3 days after abrasion. Moreover, we did not observe a difference in the epithelial closure time upon OPA1 mutation.…”

“…Because a change in tear film composition should reflect a lacrimal gland defect, and/or a subsequent modification of corneal physiology, we hypothesized that in our model any changes with the corneal epithelium would have to be subtle. Therefore, we investigated the transcriptomic signature of the cornea, which has proven before to be a solid indicator of corneal physiology 44,49,50 . As suggested by the unaffected tear film, the transcriptomic signature was largely normal, and all the corneal epithelial identity genes, such as krt14 , krt3 , krt12 , pax6 were not influenced by OPA1 mutation.…”