scholarly journals The opioid peptide biphalin modulates human corneal epithelial wound healing in vitro

Author(s):  
O.M. Gedar Totuk ◽  
E. Yildiz ◽  
A. Mollica ◽  
K. Kabadayi ◽  
A. Sahin
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.


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.


1993 ◽  
Vol 6 (2) ◽  
pp. 96-103 ◽  
Author(s):  
Steven S. Matsumoto ◽  
Michael E. Stern ◽  
Roger M. Oda ◽  
Corine R. Ghosn ◽  
Josephine W. Cheng ◽  
...  

2006 ◽  
Vol 47 (5) ◽  
pp. 1862 ◽  
Author(s):  
Masanao Watanabe ◽  
Shoichi Kondo ◽  
Ken Mizuno ◽  
Wataru Yano ◽  
Hiroshi Nakao ◽  
...  

NanoImpact ◽  
2020 ◽  
Vol 17 ◽  
pp. 100198 ◽  
Author(s):  
Soohyun Kim ◽  
Brooke L. Gates ◽  
Brian C. Leonard ◽  
Megan M. Gragg ◽  
Kent E. Pinkerton ◽  
...  

2021 ◽  
Author(s):  
Xuran Li ◽  
Xiaolong Liu ◽  
Yanyan Zhang ◽  
Zhiyu Liu ◽  
Xinyue Li ◽  
...  

Abstract BackgroundRapid restoration of corneal epithelium integrity after injury is particularly important for preserving corneal transparency and vision. Mesenchymal stem cells (MSCs) can be taken into account as the promising regenerative therapeutics for improvement of wound healing processes based on the variety of the effective components. The extracellular vesicles form MSCs, especially exosomes, has been considered as important paracrine mediators though transferring microRNAs into recipient cell. This study investigated the mechanism of human umbilical cord MSC-derived exosomes (HUMSC-exosomes) on corneal epithelial wound healing.MethodsExosomes extracted from HUMSCs were identified by transmission electron microscopy, nanoparticle tracking analysis, and Western blot. Corneal fluorescein staining and histological staining were evaluated in a corneal mechanical wound model. Changes in HCECs proliferation after HUMSC-exosomes or miR-21 mimic treatment were evaluated by CCK-8 and EdU assays, while migration was assessed by in vitro scratch wound assay. Full-length transcriptome sequencing was performed to identify the differentially expressed genes associated with HUMSC-exosomes treatment, followed by validation via real-time PCR and Western blot.ResultsThe exosomes derived from HUMSCs can significantly promote corneal epithelial cells proliferation, migration in vitro and accelerate corneal epithelial wound healing in vivo. Similar effects were obtained after miR-21 transfection, while the beneficial effects of HUMSC-exosomes were partially negated by miR-21 knockdown. Results also show that the benefits are associated with decreased PTEN level and activated the PI3K/Akt signaling pathway in HCECs.ConclusionsHUMSC-exosomes could accelerate the recovery of corneal epithelial wounds though restraining PTEN by transferring miR-21, and may represent a promising novel therapeutic agent for corneal wound repair.


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