scholarly journals Unilateral zebrafish corneal injury induces bilateral cell plasticity supporting wound closure

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Kaisa Ikkala ◽  
Vassilis Stratoulias ◽  
Frederic Michon
Keyword(s):  
Wound Healing ◽  
Wound Closure ◽  
Tgf Beta ◽  
Cell Plasticity ◽  
Corneal Epithelial ◽  
Corneal Injury ◽  
Molecular Events ◽  
Organ Regeneration ◽  
Receptor Inhibition ◽  
Corneal Wound

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.

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
Keyword(s):  
Wound Healing ◽  
Wound Closure ◽  
Profound Change ◽  
Corneal Wound Healing ◽  
Organ Regeneration ◽  
Corneal Wound ◽  
Aquatic Vertebrates ◽  
Transcriptomic Signature ◽  
Speed Up ◽  
First Time

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.

A nano-phytochemical ophthalmic solution for marked improvement of corneal wound healing in healthy or diabetic mice

Nanomedicine ◽  
2021 ◽  
Author(s):  
Qiqi Li ◽  
Meng Xin ◽  
Xianggen Wu ◽  
Bo Lei
Keyword(s):  
Wound Healing ◽  
Ophthalmic Solution ◽  
Diabetic Mice ◽  
Promoting Effect ◽  
Related Factors ◽  
Corneal Wound Healing ◽  
Corneal Epithelial ◽  
Trigeminal Neurons ◽  
Corneal Wound

Aim: To formulate a novel nano-phytochemical ophthalmic solution to promote corneal wound healing. Methods: Dipotassium glycyrrhizinate (DG) and palmatine (PAL) were used to formulate this formulation marked as DG-PAL, and its efficacy and mechanisms for promoting corneal wound healing were evaluated in mice. Results: DG-PAL was easily fabricated with excellent physical profiles. In in vivo efficiency evaluations, DG-PAL demonstrated an excellent promoting effect on corneal epithelial/nerve wound healing in both healthy and diabetic mice. These effects were involved in the DG-PAL-induced decreased expression levels of HMGB1 and its signaling-related factors in the corneas and trigeminal neurons of the healthy or diabetic mice. Conclusion: DG-PAL possibly represents a promising ophthalmic solution for promoting corneal wound healing.

scholarly journals Cannabinoid CB2R receptors are upregulated with corneal injury and regulate the course of corneal wound healing

2019 ◽  
Vol 182 ◽  
pp. 74-84 ◽  
Author(s):  
Natalia Murataeva ◽  
Sally Miller ◽  
Amey Dhopeshwarkar ◽  
Emma Leishman ◽  
Laura Daily ◽  
...  
Keyword(s):  
Wound Healing ◽  
Corneal Wound Healing ◽  
Corneal Injury ◽  
Corneal Wound

scholarly journals Caveolin-1 regulates corneal wound healing by modulating Kir4.1 activity

2016 ◽  
Vol 310 (11) ◽  
pp. C993-C1000 ◽  
Author(s):  
Chengbiao Zhang ◽  
Xiaotong Su ◽  
Lars Bellner ◽  
Dao-Hong Lin
Keyword(s):  
Wound Healing ◽  
Epithelial Cells ◽  
Western Blot ◽  
Negative Control ◽  
Promoting Effect ◽  
Corneal Epithelial Cells ◽  
Corneal Wound Healing ◽  
Corneal Epithelial ◽  
Caveolin 1 ◽  
Corneal Wound

The expression of caveolin-1 (Cav1) in corneal epithelium is associated with regeneration potency. We used Cav1−/− mice to study the role of Cav1 in modulating corneal wound healing. Western blot and whole cell patch clamp were employed to study the effect of Cav1 deletion on Kir4.1 current density in corneas. We found that Ba2+-sensitive K+ currents in primary cultured murine corneal epithelial cells (pMCE) from Cav1−/− were dramatically reduced (602 pA) compared with those from wild type (WT; 1,300 pA). As a consequence, membrane potential was elevated in pMCE from Cav1−/− compared with that from WT (−43 ± 7.5 vs. −58 ± 4.0 mV, respectively). Western blot showed that either inhibition of Cav1 expression or Ba2+ incubation stimulated phosphorylation of the EGFR. The transwell migration assay showed that Cav1 genetic inactivation accelerated cell migration. The regrowth efficiency of human corneal epithelial cells (HCE) transfected with siRNA-Cav1 or negative control was evaluated by scrape injury assay. With the presence of mitomycin C (10 μg/ml) to avoid the influence of cell proliferation, Cav1 inhibition with siRNA significantly increased migration compared with control siRNA in HCE. This promoting effect by siRNA-Cav1 could not be further enhanced by cotransfection with siRNA-Kcnj10. By using corneal debridement, we found that wound healing was significantly accelerated in Cav1−/− compared with WT mice (70 ± 10 vs. 36 ± 3%, P < 0.01). Our findings imply that the mechanism by which Cav-1 knockout promotes corneal regrowth is, at least partially, due to the inhibition of Kir4.1 which stimulates EGFR signaling.

scholarly journals Hyaluronate Acid-Dependent Protection and Enhanced Corneal Wound Healing against Oxidative Damage in Corneal Epithelial Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Jing Zhong ◽  
Yuqing Deng ◽  
Bishan Tian ◽  
Bowen Wang ◽  
Yifang Sun ◽  
...  
Keyword(s):  
Wound Healing ◽  
Cell Migration ◽  
Epithelial Cells ◽  
Cell Apoptosis ◽  
Corneal Epithelial Cell ◽  
Corneal Epithelial Cells ◽  
Corneal Wound Healing ◽  
Corneal Epithelial ◽  
Expression Levels ◽  
Corneal Wound

Purpose. To evaluate the effects and mechanism of exogenous hyaluronate (HA) in promoting corneal wound healing.Methods. Human corneal epithelial cells (HCECs) were incubated with different concentrations of HA to evaluate their efficiency in promoting cell migration and their modulation of repair factors. After inducing hyperosmolar conditions, the cell morphologies, cell apoptosis, and expression levels of TNF-αand MMP-9 were detected to assess the protective role of HA. Corneal epithelium-injured rat models were established to test the therapeutic effects of 0.3% HA. Then, the wound healing rates, the RNA expression levels of inflammatory cytokines, and repair factors were examined.Results. HCECs in the 0.03% and 0.3% HA groups showed fewer morphological alterations and lower rates of cell apoptosis following preincubation with HA under hyperosmolar conditions, as well as the expression levels of MMP-9 and TNF-α. In the rat model, the areas of fluorescein staining in the corneas of 0.3% HA group were significantly smaller than the control group. The expression levels of IL-1βand MMP-9 were decreased, while CD44 and FN were increased in the 0.3% HA group.Conclusion. HA enhanced corneal epithelial cell wound healing by promoting cell migration, upregulating repair responses, and suppressing inflammatory responses.

scholarly journals Potential role of corneal epithelial cell-derived exosomes in corneal wound healing and neovascularization

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Kyu-Yeon Han ◽  
Jennifer A. Tran ◽  
Jin-Hong Chang ◽  
Dimitri T. Azar ◽  
James D. Zieske
Keyword(s):  
Wound Healing ◽  
Epithelial Cell ◽  
Potential Role ◽  
Corneal Epithelial Cell ◽  
Corneal Wound Healing ◽  
Corneal Epithelial ◽  
Corneal Wound
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