Metformin activity in an in vitro model of posterior capsule opacification

• Main Authors: Jade Marie Lasiste, Pablo Zoroquiain, Denise Miyamoto, Miguel N Burnier
• Format: Article
• Language: English
• Published: Wolters Kluwer Medknow Publications 2018-01-01
• Series: The Pan-American Journal of Ophthalmology
• Subjects: metformin; lens epithelial cells; posterior capsule opacification; epithelial-to-mesenchymal transition.
• Online Access: http://www.thepajo.org/article.asp?issn=2666-4909;year=2018;volume=17;issue=4;spage=105;epage=112;aulast=Lasiste;type=0
• ISSN: 2666-4909; 2666-4909

Purpose: To determine the activity of metformin in an in vitro model of posterior capsule opacification (PCO). Study Design: Experimental laboratory research. Methods: The HLE-B3 lens epithelial cell line was treated with PCO induction media (PCOM) supplemented with transforming growth factor-beta (TGF-β) and fibro-blast growth factor (FGF). Different metformin concentrations (0-100 mM) were used. The following cellular parameters were assessed: (1) survival, using a viability assay; (2) morphology, via microscopy and image analysis; (3) migration, using the wound assay; (4) and expression of epithelial (Pax6, E-cadherin) and mesenchymal (α-smooth muscle actin or α-SMA, fibronectin) markers via Western blot. Expression of the uptake receptor SLC22A1 was evaluated in HLE-B3 and in human donor eyes with Western blot and immunohistochemistry, respectively. Statistical analysis of variance (ANOVA) with Tukey post-hoc test was done for analysis of cytotoxicity, morphology and migration data. Results: Metformin was lethal to half (LC50) of the cells at 30 mM, and a decrease in viability (P<0.05) was noted at 5 mM. LECs in PCOM treated with 1 mM metformin showed increased Pax6 and E-cadherin and decreased α-SMA and fibronectin expression. LECs in PCOM treated with metformin also maintained epithelial morphology. Migration was inhibited with 0.5 mM metformin (P<0.05). Both HLE-B3 and the lens epithelium in donor eyes were found to express SLC22A1. Conclusion: Metformin decreased survival and migration in LECs, maintaining epithelial phenotype and reducing mesenchymal marker expression. Metformin therefore has potential as an adjunct in PCO prevention.