Abstract
Purpose: :
Posterior capsule opacification (PCO) is the most frequent complication after cataract surgery associated with a significant decrease in central vision. Erlotinib, a selective EGF-Tyrosin-Kinase-1 (HER1, EGFR1) inhibitor, is approved for treatment of neoplastic diseases and is of interest as an agent for PCO prophylaxis. In this in vitro study, Erlotinib was evaluated for biocompatibility in the anterior and posterior segment of the eye and its effect on human lens cell proliferation, migration, 3D matrix contraction and spreading in vitro.
Methods: :
To exclude toxic effects of Erlotinib, biocompatibility was assessed on five human cell types with the tetrazolium dye-reduction test (MTT) and the Live-Dead Assay: Corneal endothelial cells (CEC) and lens epithelial cells (HLE-B3) were used for the anterior segment and Müller glial cells (Mio-M1), ARPE 19 and primary RPE cells for the posterior segment. To evaluate the efficacy of Erlotinib for PCO prophylaxis, human lens epithelial cells (HLE-B3) were incubated with different non-toxic concentrations of Erlotinib to determine the IC50 concentration. In addition, EGF-chemotactic migration was analysed using the Boyden chamber assay and chemokinetic migration was determined by time lapse microscopy. Contraction was evaluated with a 3D collagen matrix contraction assay and cell spreading was assessed on fibronectin coated surfaces.
Results: :
The maximum non-toxic concentration of Erlotinib in our cell culture models was determined to be 100 µM. Erlotinib potently inhibits human lens epithelial cell proliferation with an IC50 of 10 µM in vitro (8.8µM ± 0.9 µM SD; p=0.03). Chemotactic cell migration (p = 0.004) and chemokinetic cell migration (p = 0.001) were reduced significantly in a concentration-dependant manner. Erlotinib prevents cells from collagen matrix contraction significantly (p = 0.001). Also, the cells ability for spreading as a measure for early adhesion is decreased (p = 0.001). All effects occurred in a non-toxic concentration interval.
Conclusions: :
Erlotinib is highly biocompatible in the anterior and posterior segment of the eye. As a specific inhibitor of the EGFR receptor, it has the potential for preventing posterior capsule opacification formation in vitro. Further studies are needed to evaluate Erlotinib before it can be applied clinically.
Keywords: posterior capsular opacification (PCO) • growth factors/growth factor receptors • enzymes/enzyme inhibitors