scholarly journals β-blocker eye drops affect ocular surface through β2 adrenoceptor of corneal limbal stem cells

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xingyue Yuan ◽  
Xiubin Ma ◽  
Lingling Yang ◽  
Qingjun Zhou ◽  
Ya Li
Keyword(s):  
Wound Healing ◽  
Ocular Surface ◽  
Eye Drops ◽  
Limbal Stem Cells ◽  
Corneal Wound Healing ◽  
Corneal Epithelial ◽  
Epithelial Wound Healing ◽  
Corneal Wound ◽  
Specific Antagonist ◽  
Β Blocker

Abstract Background Topical application of β-blocker eye drops induces damage to the ocular surface in clinical. However, the mechanism involved remains incompletely understood. The purpose of this study was to investigate the influence and mechanism of β-blocker eye drops on corneal epithelial wound healing. Methods Corneal epithelial wound healing models were constructed by epithelial scraping including in the limbal region and unceasingly received eye drops containing 5 mg/mL β-blocker levobunolol, β1-adrenoceptor (β1AR)-specific antagonist atenolol or β2-adrenoceptor (β2AR)-specific antagonist ICI 118, 551. For the migration assay, the murine corneal epithelial stem/progenitor cells (TKE2) were wounded and subsequently incubated with levobunolol, atenolol, or ICI 118, 551. The proliferation and colony formation abilities of TKE2 cells treated with levobunolol, atenolol, or ICI 118, 551 were investigated by CCK-8 kit and crystal violet staining. The differentiation marker Cytokeratin 3 (CK3), the stem cell markers-Cytokeratin 14 (CK14) and Cytokeratin 19 (CK19), and corneal epithelium regeneration-related signaling including in Ki67 and the phosphorylated epithelial growth factor receptor (pEGFR) and phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) were assessed by immunofluorescence staining. Results Levobunolol and ICI 118, 551 impaired corneal wound healing, decreased the expressions of CK3, CK14, and CK19 after limbal region scraping in vivo and reduced the migration and proliferation of TKE2 in vitro, whereas atenolol had no significant effect. Moreover, levobunolol and ICI 118, 551 inhibited corneal wound healing by mediating the expression of Ki67, and the phosphorylation of EGFR and ERK1/2 in the limbal and regenerated corneal epithelium. Conclusion β-blocker eye drops impaired corneal wound healing by inhibiting the β2AR of limbal stem cells, which decreased corneal epithelial regeneration-related signaling. Therefore, a selective β1AR antagonist might be a good choice for glaucoma treatment to avoid ocular surface damage.

Corneal Epithelial Deficiency Induced by the Use of β-Blocker Eye Drops

1997 ◽  
Vol 7 (4) ◽  
pp. 334-339 ◽  
Author(s):  
Y. Haruta ◽  
Y. Ohashi ◽  
S. Matsuda
Keyword(s):  
Wound Healing ◽  
Physiological Saline ◽  
Eye Drops ◽  
Term Study ◽  
Corneal Epithelial ◽  
Long Term Study ◽  
Short Term Study ◽  
Epithelial Wound Healing ◽  
Β Blocker

Two studies were conducted to check the effects of β-blocker eye drops, 2% carteolol (Mikelan®) and 0.5% timolol (Timoptol®), on regeneration of corneal epithelium in rabbit eyes. For the short-term study, epithelial deficiency was artificially induced in the cornea of albino rabbits. One of the β-blocker eye drops or 0.005% benzalkonium chloride was applied in the right eye and physiological saline solution was applied to the left eye four times a day, and wound healing rate was calculated. Two weeks later, images of the surface epithelium were analyzed by scanning electron microscopy and proliferative capacity was studied, using proliferating cell nuclear antigen as a marker. The long-term study was conducted similarly except that the eye drops were applied twice a day and epithelial deficiency was re-induced every two weeks. In the short-term study, epithelial wound healing rate was slowed in β-blocker groups. Significant differences were detected between the Mikelan® and Timoptol® groups, and the benzalkonium and physiological saline groups. The β-blocker groups had severe epithelial cell desquamation, as well as detachment. In the long-term study, the Mikelan® group had significantly delayed wound healing at first induction, the benzalkonium group showed delay up to the third induction and the Timoptol® group up to the fifth induction. These studies indicate that β-blocker eye drops delay corneal epithelial wound healing and supported the concept that corneal epithelial deficiency occurs clinically after the long-term administration of β-blocker eye drops.

scholarly journals SFTA3 – a novel surfactant protein of the ocular surface and its role in corneal wound healing and tear film surface tension

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Martin Schicht ◽  
Fabian Garreis ◽  
Nadine Hartjen ◽  
Stephanie Beileke ◽  
Christina Jacobi ◽  
...  
Keyword(s):  
Surface Tension ◽  
Wound Healing ◽  
Ocular Surface ◽  
Tear Film ◽  
Film Surface ◽  
Surfactant Protein ◽  
Corneal Wound Healing ◽  
Corneal Wound

A nano-phytochemical ophthalmic solution for marked improvement of corneal wound healing in healthy or diabetic mice

Nanomedicine ◽  
2021 ◽  
Author(s):  
Qiqi Li ◽  
Meng Xin ◽  
Xianggen Wu ◽  
Bo Lei
Keyword(s):  
Wound Healing ◽  
Ophthalmic Solution ◽  
Diabetic Mice ◽  
Promoting Effect ◽  
Related Factors ◽  
Corneal Wound Healing ◽  
Corneal Epithelial ◽  
Trigeminal Neurons ◽  
Corneal Wound

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.

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

2016 ◽  
Vol 310 (11) ◽  
pp. C993-C1000 ◽  
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.

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 ◽  
...  
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.

Germinal peptide eye drops promote corneal wound healing and decrease inflammation after alkali injury

2020 ◽  
Vol 199 ◽  
pp. 108191
Author(s):  
Jieying Guan ◽  
Lijia Zhou ◽  
Li Wang ◽  
Xiaoyi Li ◽  
Zhiqiang Pan
Keyword(s):  
Wound Healing ◽  
Eye Drops ◽  
Corneal Wound Healing ◽  
Corneal Wound ◽  
Alkali Injury
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