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Graefe's Archive for Clinical and Experimental Ophthalmology
Erschienen in: Graefe's Archive for Clinical and Experimental Ophthalmology 6/2013

01.06.2013 | Cataract

EGF receptor inhibitor erlotinib as a potential pharmacological prophylaxis for posterior capsule opacification

verfasst von: C. Wertheimer, R. Liegl, M. Kernt, W. Mayer, D. Docheva, A. Kampik, K. H. Eibl-Lindner

Erschienen in: Graefe's Archive for Clinical and Experimental Ophthalmology | Ausgabe 6/2013

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Abstract

Background

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

Methods

To exclude toxic concentrations, erlotinib was assessed for its biocompatibility on five different human ocular cell types in vitro by the tetrazolium dye-reduction assay (MTT) and the Live–Dead assay. To determine its effect on human lens epithelial cell (HLE-B3) proliferation, the MTT test was performed after incubation with different concentrations of erlotinib. Chemotactic migration was analyzed with the Boyden chamber assay and chemokinetic migration was assessed by time lapse microscopy. Contraction was measured by a 3D collagen type 1 matrix contraction assay, and cell spreading was determined by measuring the cell diameter on a fibronectin coated surface.

Results

The maximum non-toxic concentration of erlotinib was determined to be 100 μM in cell culture. Erlotinib potently inhibits human lens epithelial cell proliferation, with an IC50 of about 10 μM (8.8 μM ± 0.9 μM SD; r 2 = 0.94). Chemotactic migration (p = 0.004) and chemokinetic migration (p = 0.001) were reduced significantly in a concentration-based manner. Erlotinib prevented human lens epithelial cells from matrix contraction (p = 0.001) and cell-spreading (p = 0.001).

Conclusions

Erlotinib might become of clinical relevance for PCO prophylaxis in the future since it displayed good biocompatibility on ocular cells and mitigated human lens epithelial cell proliferation, migration, contraction, and spreading in vitro. Further studies are warranted to evaluate its potential for clinical application.
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Metadaten
Titel
EGF receptor inhibitor erlotinib as a potential pharmacological prophylaxis for posterior capsule opacification
verfasst von
C. Wertheimer
R. Liegl
M. Kernt
W. Mayer
D. Docheva
A. Kampik
K. H. Eibl-Lindner
Publikationsdatum
01.06.2013
Verlag
Springer-Verlag
Erschienen in
Graefe's Archive for Clinical and Experimental Ophthalmology / Ausgabe 6/2013
Print ISSN: 0721-832X
Elektronische ISSN: 1435-702X
DOI
https://doi.org/10.1007/s00417-013-2257-z

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