EGF-Receptor Inhibitors Erlotinib and Gefitinib mitigate posterior capsule opacification in the human capsular bag model.

Abstract

Purpose: Posterior capsule opacification (PCO) occurs as a common complication after previous cataract surgery. Erlotinib and Gefitinib are selective inhibitors of the EGF-Receptor, which represents a potential pharmacological target for PCO prevention. Both inhibitors were effective in two different human lens epithelial cell lines, with good biocompatibility. In this in vitro study, we assessed the effect of Erlotinib and Gefitinib on PCO prevention in the human capsular bag model.

Methods: For the human capsular bag model, 32 cadaver eyes from sixteen human donors underwent sham cataract surgery. Methods for securing human tissue were humane, included proper consent and approval, complied with the Declaration of Helsinki and were approved by the local ethics committee. The capsular bag was removed and transferred into cell culture. The tissue was exposed to the previously determined IC50 of Erlotinib (10 µM) and Gefitinib (10 µM) for 72 hrs, solvent only served as control. Cellular growth was observed over 30 days and foto-documented.

Results: Erlotinib (p<0.001) and Gefitinib (p<0.001) increased the time until confluence of the capsular bag significantly compared to controls. The control reached confluence in 5.4 days. Erlotinib at its IC50 prolonged the growth to 12 days and Gefitinib to 11 days.

Conclusions: Erlotinib and Gefitinib induced a long-term attenuation of cellular growth in the human capsular bag model after being added for a short time period after preparation. Both inhibitors might become of clinical relevance in PCO prophylaxis. The potential role of EGFR-inhibition in PCO prophylaxis was highlighted.

Keywords: 652 posterior capsular opacification (PCO) • 445 cataract • 765 wound healing