Lidocaine blocks the proliferation, Migration, and Epithelial‐Mesenchymal Transition of Human Retinal Epithelial cells

Abstract

IntroductionProliferative vitroretinopathy (PVR) is a major cause of failure in surgery of rhegmatogenous retinal detachment (RRD). The incidence of PVR approximately attains up to 5~10% of RDD and 75% of redetachment after surgery, however, the strategy for precautions or resolving the PVR is very limited. Lidocaine is well known and widely used local anesthetics. We evaluated the effects of lidocaine on epithelial‐mesenchymal transition (EMT) and migration in retinal pigment epithelial cells, which is major cell type involved in the development of PVR, and its mechanism.MethodsAdult retinal pigmented epithelial 19 (ARPE 19) cell line was used and MTT (3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐Diphenyltetrazolium Bromide) assay was performed with various concentrations of lidocaine. We induced ARPE to EMT by TGFβ‐1 and it was demonstrated with western blot of α‐SMA (smooth muscle actin), vimentin, E‐cadherin, and collagen I. The inhibitory effects of lidocaine in TGFβ‐1 signaling were also evaluated with western blot of ERK (extracellular signal regulated kinase), PI3K (Phosphoinositide 3‐kinase), Akt (Protein kinase B), and smad. The change of motile activity by TGFβ‐1 and lidocaine was demonstrated with migration assay.ResultsLidocaine was inhibited the proliferation of ARPE cells in concentration dependent manner after treatment of lidocaine, 24 hours and 48 hours, respectively. Migration activity of ARPE cells were inhibited by lidocaine and the migration of ARPE cells undergoing EMT by TGFβ‐1 was also inhibited significantly. Lidocaine prevented EMT by decreasing the activations of ERK, PI3K, Akt and smad, result in decreasing the expression of α‐SMA, vimentin, and collagen I synthesis and increasing the expression of E‐cadherin.ConclusionsLidocaine blocks the proliferation, migration, and EMT of ARPE cells by inhibition of TGFβ‐1 signaling pathway.Support or Funding InformationThis work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean Government (NRF‐2017R1C1B5017925).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.