Affiliation:
1. Postgraduate Student.
2. Clinical Fellow.
3. Research Assistant.
4. Assistant Professor, Department of Ophthalmology, Kyoto Prefectural University of Medicine.
5. Instructor.
6. Associate Professor, Graduate School of Pharmaceutical Sciences, Kyoto University.
7. Assistant Professor, Department of Anesthesiology.
Abstract
Background
Although lidocaine is recognized as an excellent topical corneal analgesic, its toxic effect on corneal epithelial cells limits its use during corneal epithelial wound healing. Mechanism of the impairment of corneal reepithelialization with lidocaine, however, has not been evaluated. The authors' previous study revealed that lidocaine inhibits the activity of tyrosine kinase receptors through the interaction with specific amino acid sequences around autophosphorylation sites, including acidic, basic, and aromatic amino acids. Epidermal growth factor receptor (EGFR), a tyrosine kinase receptor with an important role in epithelial cell proliferation after corneal wounding, also possesses these amino acids sequences around autophosphorylation sites. The authors hypothesized that lidocaine would suppress tyrosine kinase activity of EGFR and would impair corneal epithelial cell proliferation.
Methods
To investigate the effect of lidocaine (4 microM-40 mM) on epidermal growth factor (EGF)-stimulated autophosphorylation of EGFR, the authors studied purified EGFR in microtubes. They cultured human corneal epithelial cells (HCECs) with EGF and lidocaine to investigate the effect of lidocaine on cell proliferation and on autophosphorylation of EGFR in HCECs.
Results
Lidocaine (> or =400 microM) significantly suppressed EGF-stimulated autophosphorylation of the purified EGFR. In the HCEC study, EGF alone stimulated cell proliferation and increased autophosphorylation of EGFR in HCECs. Lidocaine (> or = 400 microM) significantly suppressed both the proliferation of HCECs promoted by EGF and EGF-stimulated autophosphorylation of EGFR.
Conclusion
Lidocaine directly inhibits tyrosine kinase activity of EGFR and suppresses the corneal epithelial cell proliferation.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Anesthesiology and Pain Medicine
Cited by
31 articles.
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