Corneal Epithelial Wound Healing Promoted by Verbascoside-Based Liposomal Eyedrops

Different liposomal formulations were prepared to identify those capable of forming eyedrops for corneal diseases. Liposomes with neutral or slightly positive surface charge interact very well with the cornea. Then these formulations were loaded with verbascoside to heal a burn of corneal epithelium induced by alkali. The cornea surface affected involved in wound was monitored as a function of time. Experimental results were modeled by balance equation between the rate of healing, due to the flow of phenylpropanoid, and growth of the wound. The results indicate a latency time of only three hours and furthermore the corneal epithelium heals in 48 hours. Thus, the topical administration of verbascoside appears to reduce the action time of cells, as verified by histochemical and immunofluorescence assays.

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Impact of Different Oxygen Supply Methods on the Healing of Corneal Epithelial Wound and the Level of Acetylcholine

Journal of Ophthalmology ◽

10.1155/2021/4737479 ◽

2021 ◽

Vol 2021 ◽

pp. 1-6

Author(s):

Shanshan Li ◽

Gang Ding ◽

Yuqin Sun ◽

Chenming Zhang

Keyword(s):

Wound Healing ◽

Oxygen Concentration ◽

Corneal Epithelium ◽

Oxygen Supply ◽

Low Flow ◽

Corneal Epithelial ◽

Epithelial Wound Healing ◽

Acetylcholine Level ◽

Group A ◽

Group B

Purpose. To investigate the impact of different oxygen supply methods on corneal epithelial wound healing and acetylcholine level during wound healing. Methods. We randomly divided 75 rabbits into three groups: A, B, and C, with 25 rabbits in each group. The central corneal epithelium was removed from all eyes of the rabbits using a 5 mm trephine. Group A rabbits were given low flow oxygen (3 L/min; concentration: 33%) for 2 h per day through goggles. Group B rabbits were given low flow oxygen (3 L/min; concentration: 33%) for 2 h per day via oxygen masks for inhalation. Group C rabbits healed naturally. The area of healed corneal epithelium and acetylcholine content in corneal epithelium were determined at 12 h, 24 h, and 36 h after injury. Results. At 12 h, 24 h, and 36 h after injury, the healing area of corneal epithelium in the three groups was in the order group A > group B > group C ( P < 0.05 ). At all timepoints, the acetylcholine level in corneal epithelium was in the order of group A > group B > group C ( P < 0.05 ). In all three groups, the acetylcholine content in corneal epithelium showed the order 12 h > 24 h > 36 h ( P < 0.05 ). There was a correlation between acetylcholine expression and the area of unhealed corneal epithelium, and the correlation coefficients of groups A, B, and C were 0.80, 0.83, and 0.85 respectively. Conclusion. Increasing oxygen concentration through inhalation or via goggles can promote corneal epithelial wound healing, but increasing local oxygen concentration of the eye showed a better effect. Acetylcholine may play an important role in the early process of corneal epithelial wound healing.

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

10.21203/rs.2.11471/v1 ◽

2019 ◽

Author(s):

Ozgun Melike Gedar Totuk ◽

Erdost YILDIZ ◽

Adriano MOLLICA ◽

Kerem KABADAYI ◽

Afsun SAHIN

Keyword(s):

Wound Healing ◽

Corneal Epithelium ◽

Wound Closure ◽

Opioid Peptide ◽

Corneal Epithelial Cell ◽

Scratch Assay ◽

Corneal Epithelial ◽

Significant Difference ◽

Epithelial Wound Healing

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.

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

10.21203/rs.2.11471/v2 ◽

2020 ◽

Author(s):

Ozgun Melike Gedar Totuk ◽

Erdost YILDIZ ◽

Adriano MOLLICA ◽

Kerem KABADAYI ◽

Afsun SAHIN

Keyword(s):

Wound Healing ◽

Corneal Epithelium ◽

Wound Closure ◽

Opioid Peptide ◽

Corneal Epithelial Cell ◽

Scratch Assay ◽

Corneal Epithelial ◽

Significant Difference ◽

Epithelial Wound Healing

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.

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Effects of Biphalin on Corneal Epithelial Wound Healing

Proceedings ◽

10.3390/proceedings2251552 ◽

2018 ◽

Vol 2 (25) ◽

pp. 1552 ◽

Cited By ~ 1

Author(s):

Erdost Yıldız ◽

Özgün Melike Gedar Totuk ◽

Adriano Mollica ◽

Kerem Kabadayı ◽

Afsun Şahin

Keyword(s):

Wound Healing ◽

Mtt Assay ◽

Corneal Epithelium ◽

Healing Process ◽

Wound Healing Process ◽

Corneal Epithelial ◽

Positive Effects ◽

Study Results ◽

Significant Difference ◽

Epithelial Wound Healing

After physical or surgical damage of corneal epithelium, most of analgesic drugs, like non-selective opioid agonists and non-steroid anti-inflammatory drugs, cannot be used because of their negative effects on wound healing process. Biphalin is selective µ and Δ opioid receptor agonist which has proven analgesic effects on rodents. Our purpose of study is finding effects of biphalin on wound healing of corneal epithelium. We used primary culture of human corneal epithelial cells (HCECs) for examining effects of biphalin on wound healing. Firstly, we measured toxicity of Biphalin in various concentrations with MTT assay and we showed biphalin has no toxic effects on HCECs in lower concentrations than 100 µM in various incubation times. After MTT assay, we administered 1 µM and 10 µM biphalin at in vitro scratch assay of HCECs, biphalin increased wound closure process significantly at 1 µM concentration (p < 0.05). Then we tested effects of biphalin on cell migration and proliferation separately. Bifalin increased migration of HCECs significantly (p < 0.01) at transwell migration assay. But we did not observe any significant difference between groups in Ki67 proliferation assay. In all these experiments, we also used naloxone to inhibiting effects of biphalin. In biphalin plus naloxone groups, effects of biphalin decrease partially. Our study results suggest, biphalin has positive effects on epithelial wound healing via opioid receptors. This effect because of increased migration of HCECs under influence of biphalin. With these findings, we propose biphalin as a new analgesic agent for post-surgical and post-traumatic care of corneal epithelial wounds.

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