ArticleBMC ophthalmology2021
β-blocker eye drops affect ocular surface through β2 adrenoceptor of corneal limbal stem cells.
Article in BMC ophthalmology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 14 citations in OpenAlex.
- Limbal stem cell deficiency secondary to topical glaucoma medication: a scoping review.International journal of ophthalmology · 2026Review
- Amine-responsive Rhodopsin-like GPCRs in ocular pathology: mechanistic associations, candidate biomarkers, and therapeutic potential.Frontiers in physiology · 2026Review
- Conditioned media of stem cells from human exfoliated deciduous teeth contain factors related to extracellular matrix organization and promotes corneal epithelial wound healing.Regenerative therapy · 2025Article
- Norepinephrine regulates epithelial-derived neurotrophins expression and sensory nerve regeneration through ADRB2 receptor.Communications biology · 2025Article
- Managing Ocular Surface Disease in Glaucoma Treatment: A Systematic Review.Bioengineering (Basel, Switzerland) · 2024Review
- The βAdvances in pharmacological and pharmaceutical sciences · 2024Review
- Adrenoceptors in the Eye - Physiological and Pathophysiological Relevance.Handbook of experimental pharmacology · 2024Review
- Stable Gastric Pentadecapeptide BPC 157-Possible Novel Therapy of Glaucoma and Other Ocular Conditions.Pharmaceuticals (Basel, Switzerland) · 2023Review
- β-Adrenoreceptors as Therapeutic Targets for Ocular Tumors and Other Eye Diseases-Historical Aspects and Nowadays Understanding.International journal of molecular sciences · 2023Review
- A Narrative Review of Ocular Surface Disease Related to Anti-Glaucomatous Medications.Ophthalmology and therapy · 2022Review
- Activation of ADRB2/PKA Signaling Pathway Facilitates Lipid Synthesis in Meibocytes, and Beta-Blocker Glaucoma Drug Impedes PKA-Induced Lipid Synthesis by Inhibiting ADRB2.International journal of molecular sciences · 2022Article
- Glaucoma and Ocular Surface Disease: More than Meets the Eye.Clinical ophthalmology (Auckland, N.Z.) · 2022Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTopical 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.
methodsCorneal 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.
resultsLevobunolol 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.
conclusionβ-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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.