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Graefe's Archive for Clinical and Experimental Ophthalmology

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01-03-2015 | Cataract

EGFR inhibitor Gefitinib attenuates posterior capsule opacification in vitro and in the ex vivo human capsular bag model

Authors: Christian Wertheimer, Jakob Siedlecki, Daniel Kook, Wolfgang J. Mayer, Armin Wolf, Annemarie Klingenstein, Anselm Kampik, Kirsten Eibl-Lindner

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 3/2015

Abstract

Purpose

Posterior capsule opacification (PCO) occurs as a common complication after cataract surgery. Gefitinib is a selective inhibitor of the epidermal growth factor receptor (EGFR) which represents a potential pharmacological target for PCO prevention. In this in vitro study, we assessed the effect and biocompatibility of Gefitinib in PCO prophylaxis.

Methods

The effect of Gefitinib on the key pathological features of PCO was assessed in vitro. We determined growth in the human capsular bag model, prepared from sixteen cadaver eyes that underwent sham cataract surgery. Furthermore, two lens epithelial cell lines, HLE-B3 and FHL-124, were used to determine concentration-based effects on cell proliferation. In addition, cell-migration, matrix-contraction, and cell spreading were investigated. To exclude toxic concentrations, Gefitinib was assessed for its biocompatibility on six different human ocular cell types from the anterior and posterior segment of the eye.

Results

Gefitinib significantly increased the time until confluence of the capsular bag compared to controls (p < 0.001)). In both human lens epithelial cell lines (HLE-B3 and FHL-124), proliferation decreased significantly and as equally strong after incubation with Gefitinib (p < 0.001), as did chemotactic migration (p = 0.004), matrix contraction (p = 0.001), and cell-spreading (p = 0.001). At the IC₅₀ concentration, Gefitinib was well tolerated by six different human ocular cell types of the anterior and posterior segment.

Conclusion

The specific EGFR inhibitor Gefitinib might become of clinical relevance in PCO prophylaxis as it attenuated cellular growth and other pathological PCO factors in the ex vivo human capsular bag model and in two human lens epithelial cell lines, while showing good biocompatibility in vitro.

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Title: EGFR inhibitor Gefitinib attenuates posterior capsule opacification in vitro and in the ex vivo human capsular bag model
Authors: Christian Wertheimer
Jakob Siedlecki
Daniel Kook
Wolfgang J. Mayer
Armin Wolf
Annemarie Klingenstein
Anselm Kampik
Kirsten Eibl-Lindner
Publication date: 01-03-2015
Publisher: Springer Berlin Heidelberg
Published in: Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 3/2015
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI: https://doi.org/10.1007/s00417-014-2875-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

EGFR inhibitor Gefitinib attenuates posterior capsule opacification in vitro and in the ex vivo human capsular bag model

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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