EGF-Receptor inhibitor Gefitinib as a potential pharmacological prophylaxis for posterior capsule opacification

Abstract

Purpose: Posterior capsule opacification (PCO) is the most frequent complication after cataract surgery leading to a loss of sight if untreated. Gefitinib might be of therapeutic interest as an effective target agent (selective EGF-Tyrosin-Kinase-1 inhibitor) approved for cancer therapy. In this in vitro study, Gefitinib was evaluated for ocular biocompatibility and its inhibitory effects on cell proliferation, migration, 3D matrix contraction and spreading of human lens epithelial cells.

Methods: To exclude toxic concentrations, Gefitinib was assessed for its biocompatibility on five different human ocular cell types in vitro (anterior segment: lens epithelial cells (HLE-B3) and corneal endothelial cells (CEC); posterior segment: Müller glial cells (Mio-M1), ARPE 19 and primary RPE cells) by the tetrazolium dye-reduction assay (MTT) and the Live-Dead Assay. The in vitro effect of Gefitinib on human lens epithelial cells (HLE-B3) was investigated as follows: To determine its effect on cell proliferation, the MTT test was performed after the cells were incubated with different concentrations of Gefitinib. Chemotactic migration was analyzed with the Boyden Chamber Assay. Contraction was measured by a 3D matrix contraction assay with collagen type 1 gel pellets and cell spreading was investigated by measuring the cell diameter on a fibronectin coated surface.

Results: The maximum non-toxic concentration of Gefitinib was determined to be 25 µM in cell culture. Gefitinib potently inhibits human lens epithelial cell proliferation with an IC50 of about 13 µM. Migration in the Boyden Chamber Assay (p = 0.001) was reduced significantly, in a concentration based manner. Gefitinib prevented human lens epithelial cells from matrix contraction (p = 0.001) and the ability of the cells to spread on a fibronectin coated surface (p = 0.001) as a measure for early adhesion.

Conclusions: Gefitinib might become of clinical relevance for PCO prophylaxis in the future since it was demonstrated to have good biocompatibility on ocular cells and was proven effective for human lens epithelial cell proliferation, migration, contraction and spreading inhibition in vitro. Further studies are warranted to evaluate its potential for clinical application.

Keywords: 445 cataract