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 ◽  
...  

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.

2016 ◽  
Vol 310 (11) ◽  
pp. C993-C1000 ◽  
Author(s):  
Chengbiao Zhang ◽  
Xiaotong Su ◽  
Lars Bellner ◽  
Dao-Hong Lin

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.


2016 ◽  
Vol 3 (10) ◽  
pp. 160658 ◽  
Author(s):  
Amy S. Findlay ◽  
D. Alessio Panzica ◽  
Petr Walczysko ◽  
Amy B. Holt ◽  
Deborah J. Henderson ◽  
...  

This study shows that the core planar cell polarity (PCP) genes direct the aligned cell migration in the adult corneal epithelium, a stratified squamous epithelium on the outer surface of the vertebrate eye. Expression of multiple core PCP genes was demonstrated in the adult corneal epithelium. PCP components were manipulated genetically and pharmacologically in human and mouse corneal epithelial cells in vivo and in vitro . Knockdown of VANGL2 reduced the directional component of migration of human corneal epithelial (HCE) cells without affecting speed. It was shown that signalling through PCP mediators, dishevelled, dishevelled-associated activator of morphogenesis and Rho-associated protein kinase directs the alignment of HCE cells by affecting cytoskeletal reorganization. Cells in which VANGL2 was disrupted tended to misalign on grooved surfaces and migrate across, rather than parallel to the grooves. Adult corneal epithelial cells in which Vangl2 had been conditionally deleted showed a reduced rate of wound-healing migration. Conditional deletion of Vangl2 in the mouse corneal epithelium ablated the normal highly stereotyped patterns of centripetal cell migration in vivo from the periphery (limbus) to the centre of the cornea. Corneal opacity owing to chronic wounding is a major cause of degenerative blindness across the world, and this study shows that Vangl2 activity is required for directional corneal epithelial migration.


2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Kyu-Yeon Han ◽  
Jennifer A. Tran ◽  
Jin-Hong Chang ◽  
Dimitri T. Azar ◽  
James D. Zieske

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Dong Ju Kim ◽  
Mi-Young Jung ◽  
Ha-Jin Pak ◽  
Joo-Hee Park ◽  
Martha Kim ◽  
...  

AbstractOcular surface diseases (OSD) can cause serious visual deterioration and discomfort. Commercial artificial tear solution containing hyaluronic acid (HA) show excellent biocompatibility and unique viscoelastic characteristics. Here, we developed a novel HA membrane (HAM) by chemical crosslinking using 1,4-butanediol diglycidyl ether for the effective treatment of OSDs. The main purpose of HAMs is to provide sustained release of HA to modulate the wound healing response in OSDs. The safety and efficacy of HAMs were investigated using primary cultured human corneal epithelial cells and various OSD rabbit models. In the dry state, the HAM is firm, transparent, and easy to manipulate. When hydrated, it swells rapidly with high water retention and over 90% transmission of visible light. Human corneal epithelial cells and rabbit eyes showed no toxic response to HAM. Addition of HAMs to the culture medium enhanced human corneal epithelial cell viability and expression of cell proliferation markers. Investigation of HAM wound healing efficacy using mechanical or chemical corneal trauma and conjunctival surgery in rabbits revealed that application of HAMs to the ocular surface enhanced healing of corneal epithelium and reduced corneal limbal vascularization, opacity and conjunctival fibrosis. The therapeutic potential of HAMs in various OSDs was successfully demonstrated.


Eye ◽  
2017 ◽  
Vol 32 (4) ◽  
pp. 813-819 ◽  
Author(s):  
A Robciuc ◽  
R P J Arvola ◽  
M Jauhiainen ◽  
J M Holopainen

Nanomedicine ◽  
2021 ◽  
Author(s):  
Qiqi Li ◽  
Meng Xin ◽  
Xianggen Wu ◽  
Bo Lei

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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