MiRNA-155-5p Reduces Corneal Epithelial Permeability by Remodeling Epithelial Tight Junctions during Corneal Wound Healing

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.

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

AJP Cell Physiology ◽

10.1152/ajpcell.00023.2016 ◽

2016 ◽

Vol 310 (11) ◽

pp. C993-C1000 ◽

Cited By ~ 5

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.

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

Journal of Ophthalmology ◽

10.1155/2016/6538051 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 8

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.

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

Scientific Reports ◽

10.1038/srep40548 ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 31

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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Therapeutic Proteins for Treatment of Corneal Epithelial Defects

Current Medicinal Chemistry ◽

10.2174/0929867324666170609080920 ◽

2019 ◽

Vol 26 (3) ◽

pp. 517-545 ◽

Cited By ~ 6

Author(s):

Evgeni Yu. Zernii ◽

Viktoriia E. Baksheeva ◽

Elena V. Yani ◽

Pavel P. Philippov ◽

Ivan I. Senin

Keyword(s):

Wound Healing ◽

De Novo ◽

Pain Syndrome ◽

Active Components ◽

Preclinical Development ◽

Corneal Wound Healing ◽

Corneal Epithelial ◽

Corneal Scarring ◽

Corneal Wound ◽

Systemic Factors

Corneal epithelial disorders take pride of place in modern ophthalmology. Defects of corneal epithelium are commonly accompanied by blurry vision, photophobia and tearing. Since cornea is the most densely innervated tissue of organisms, its disruption leads to development of a severe pain syndrome. Mild corneal erosions commonly undergo quick spontaneous recovery. Suppression of corneal wound healing due to various pathological causes results in development of severe recurrent erosions and persistent corneal defects. These pathological events can in turn lead to corneal scarring, opacification, and ulceration of cornea, and ultimately to the permanent vision impairment. The etiology of the underlying corneal diseases that commonly involves inflammatory, neurotrophic and systemic factors, should be considered for treating such defects. Therefore, the research focus has been shifted to establish therapeutics based on proteins and peptides. Due to varied mechanisms of action, proteinbased pharmaceuticals can be involved in the protection of corneal surface, mimicking tear components, stimulation of corneal wound healing, regeneration of corneal innervation, suppressing oxidative stress, inflammation and neovascularization. The active components can be naturally occurring (blood- or tear-derived) or be created de novo and optimized in order to achieve the level of activity required. Such pharmaceuticals are characterized by low toxicity and absence of systemic side-effects due to their low absorption into the bloodstream, if administrated topically. This review summarizes existing data on protein-based drugs for treatment of corneal epithelial defects that are currently under preclinical development or testing in clinical trials, or approved for medical use.

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In Vivo Confocal Microscopic Findings of Corneal Wound Healing after Corneal Epithelial Debridement in Diabetic Vitrectomy

Ophthalmology ◽

10.1016/j.ophtha.2009.01.002 ◽

2009 ◽

Vol 116 (6) ◽

pp. 1038-1047 ◽

Cited By ~ 28

Author(s):

Wei-Li Chen ◽

Chung-Tien Lin ◽

Pei-Shou Ko ◽

Po-Ting Yeh ◽

Yi-Hsuan Kuan ◽

...

Keyword(s):

Wound Healing ◽

Corneal Wound Healing ◽

Corneal Epithelial ◽

Corneal Wound ◽

Diabetic Vitrectomy ◽

Microscopic Findings

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Corneal Epithelial–Stromal Fibroblast Constructs to Study Cell–Cell Communication in Vitro

Bioengineering ◽

10.3390/bioengineering6040110 ◽

2019 ◽

Vol 6 (4) ◽

pp. 110 ◽

Cited By ~ 4

Author(s):

Tina B. McKay ◽

Dimitrios Karamichos ◽

Audrey E. K. Hutcheon ◽

Xiaoqing Guo ◽

James D. Zieske

Keyword(s):

Wound Healing ◽

Basement Membrane ◽

Extracellular Vesicles ◽

Corneal Epithelium ◽

Cell Communication ◽

Corneal Wound Healing ◽

Corneal Epithelial ◽

Matrix Deposition ◽

Corneal Wound ◽

Cell Cell

Cell–cell communication plays a fundamental role in mediating corneal wound healing following injury or infection. Depending on the severity of the wound, regeneration of the cornea and the propensity for scar development are influenced by the acute resolution of the pro-fibrotic response mediated by closure of the wound via cellular and tissue contraction. Damage of the corneal epithelium, basement membrane, and anterior stroma following a superficial keratectomy is known to lead to significant provisional matrix deposition, including secretion of fibronectin and thrombospondin-1, as well as development of a corneal scar. In addition, corneal wounding has previously been shown to promote release of extracellular vesicles from the corneal epithelium, which, in addition to soluble factors, may play a role in promoting tissue regeneration. In this study, we report the development and characterization of a co-culture system of human corneal epithelial cells and corneal stromal fibroblasts cultured for 4 weeks to allow extracellular matrix deposition and tissue maturation. The secretion of provisional matrix components, as well as small and large extracellular vesicles, was apparent within the constructs, suggesting cell–cell communication between epithelial and stromal cell populations. Laminin-1β was highly expressed by the corneal epithelial layer with the presence of notable patches of basement membrane identified by transmission electron microscopy. Interestingly, we identified expression of collagen type III, fibronectin, and thrombospondin-1 along the epithelial–stromal interface similar to observations seen in vivo following a keratectomy, as well as expression of the myofibroblast marker, α-smooth muscle actin, within the stroma. Our results suggest that this corneal epithelial–stromal model may be useful in the study of the biochemical phenomena that occur during corneal wound healing.

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Silk films with nanotopography and extracellular proteins enhance corneal epithelial wound healing

Scientific Reports ◽

10.1038/s41598-021-87658-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yuncin Luo ◽

Kai B. Kang ◽

Rachel Sartaj ◽

Michael G. Sun ◽

Qiang Zhou ◽

...

Keyword(s):

Wound Healing ◽

Cellular Response ◽

Extracellular Proteins ◽

Collagen I ◽

Type I ◽

Corneal Wound Healing ◽

Corneal Epithelial ◽

Wound Recovery ◽

Corneal Wound ◽

Silk Films

AbstractCorneal wound healing depends on extracellular matrix (ECM) and topographical cues that modulate migration and proliferation of regenerating cells. In our study, silk films with either flat or nanotopography patterned parallel ridge widths of 2000, 1000, 800 nm surfaces were combined with ECMs which include collagen type I (collagen I), fibronectin, laminin, and Poly-d-Lysine to accelerate corneal wound healing. Silk films with 800 nm ridge width provided better cell spreading and wound recovery than other size topographies. Coating 800 nm patterned silk films with collagen I proves to optimally further increased mouse and rabbit corneal epithelial cells growth and wound recovery. This enhanced cellular response correlated with redistribution and increase in size and total amount of focal adhesion. Transcriptomics and signaling pathway analysis suggested that silk topography regulates cell behaviors via actin nucleation ARP-WASP complex pathway, which regulate filopodia formation. This mechanism was further explored and inhibition of Cdc42, a key protein in this pathway, delayed wound healing and decreased the length, density, and alignment of filopodia. Inhibition of Cdc42 in vivo resulted in delayed re-epithelization of injured corneas. We conclude that silk film nanotopography in combination with collagen I constitutes a better substrate for corneal wound repair than either nanotopography or ECM alone.

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