scholarly journals Rho kinases regulate corneal epithelial wound healing

2008 ◽  
Vol 295 (2) ◽  
pp. C378-C387 ◽  
Author(s):  
Jia Yin ◽  
Fu-Shin X. Yu

We have previously shown that Rho small GTPase is required for modulating both cell migration and proliferation through cytoskeleton reorganization and focal adhesion formation in response to wounding. In the present study, we investigated the role of Rho kinases (ROCKs), major effectors of Rho GTPase, in mediating corneal epithelial wound healing. Both ROCK 1 and 2 were expressed and activated in THCE cells, an SV40-immortalized human corneal epithelial cell (HCEC) line, in response to wounding, lysophosphatidic acid, and heparin-binding EGF-like growth factor (HB-EGF) stimulations. The ROCK inhibitor Y-27632 efficiently antagonized ROCK activities without affecting Rho activation in wounded HCECs. Y-27632 promoted basal and HB-EGF-enhanced scratch wound healing and enhanced cell migration and adhesion to matrices, while retarded HB-EGF induced cell proliferation. E-cadherin- and β-catenin-mediated cell-cell junction and actin cytoskeleton organization were disrupted by Y-27632. Y-27632 impaired the formation and maintenance of tight junction barriers indicated by decreased trans-epithelial resistance and disrupted occludin staining. We conclude that ROCK activities enhance cell proliferation, promote epithelial differentiation, but negatively modulate cell migration and cell adhesion and therefore play a role in regulating corneal epithelial wound healing.

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.


2019 ◽  
Author(s):  
Ozgun Melike Gedar Totuk ◽  
Erdost YILDIZ ◽  
Adriano MOLLICA ◽  
Kerem KABADAYI ◽  
Afsun SAHIN

Abstract Background Analgesic drugs including nonselective opioids and non-steroidal anti-inflammatory drugs should be used with great precautions to relieve the pain after physical damage of the corneal epithelium, because of their unfavorable effects on wound healing process. Biphalin, a synthetic opioid peptide, which has been demonstrated to possesses a strong analgesic effect on rodents. The purpose of this study is to investigate the effects of biphalin on human corneal epithelium wound healing. Methods Immortalized human corneal epithelial cell (HCEC) culture was used to test the effects of biphalin on wound healing. The toxicity of biphalin in various concentrations was measured with MTT assay. The effect of 1 µM and 10 µM biphalin were tested on wound closure at in vitro scratch assay of HCECs, and for cell migration and proliferation separately. Naloxone, a non-selective competitive antagonist of opioid receptor, was also used to inhibit the effects of biphalin in all experiments. Results Biphalin did not cause any toxic effect on HCECs in concentrations lower than 100 µM at various incubation time points. Biphalin increased wound closure process significantly at 1 µM concentration at in vitro scratch assay of HCECs (p < 0.05); also increased migration of HCECs significantly (p < 0.01). There was no significant difference between biphalin and control groups of HCECs at Ki67 proliferation assay. Conclusion Biphalin, a synthetic opioid peptide, has a potential role as a novel topical analgesic agent that promotes corneal epithelial wound healing.


2008 ◽  
Vol 49 (3) ◽  
pp. 900 ◽  
Author(s):  
Jia Yin ◽  
Jinshuang Lu ◽  
Fu-Shin X. Yu

2020 ◽  
Author(s):  
Ozgun Melike Gedar Totuk ◽  
Erdost YILDIZ ◽  
Adriano MOLLICA ◽  
Kerem KABADAYI ◽  
Afsun SAHIN

Abstract Background: Analgesic drugs, including nonselective opioids and non-steroidal anti-inflammatory drugs, should be used with great precautions to relieve pain after physical damage of the corneal epithelium because of their unfavorable effects on the wound-healing process. Biphalin is a synthetic opioid peptide that has been demonstrated to possesses a strong analgesic effect on rodents. The purpose of this study is to investigate the effects of biphalin on human corneal epithelium wound healing.Methods: An immortalized human corneal epithelial cell (HCEC) culture was used to test the effects of biphalin on wound healing. The toxicity of biphalin in various concentrations was measured with the MTT assay. The effect of 1 µM and 10 µM biphalin were tested on wound closure in an in vitro scratch assay of HCECs and for cell migration and proliferation separately. Naloxone, a non-selective competitive antagonist of opioid receptors, was also used to inhibit the effects of biphalin in all experiments.Results: Biphalin did not cause any toxic effect on HCECs in concentrations lower than 100 µM at various incubation time points. Biphalin increased the wound closure process significantly at 1 µM concentration in an in vitro scratch assay of HCECs (p < 0.05). It also increased the migration of HCECs significantly (p < 0.01). There was no significant difference between biphalin and control groups of HCECs in the Ki67 proliferation assay.Conclusion: Biphalin, a synthetic opioid peptide, has a potential role as a novel topical analgesic agent that promotes corneal epithelial wound healing. This role should be evaluated in further in vivo and clinical studies.


2004 ◽  
Vol 45 (4) ◽  
pp. 1125 ◽  
Author(s):  
Naoyuki Yamada ◽  
Ryoji Yanai ◽  
Masatsugu Nakamura ◽  
Makoto Inui ◽  
Teruo Nishida

Sign in / Sign up

Export Citation Format

Share Document