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Attenuation of human lens epithelial cell spreading, migration and contraction via downregulation of the PI3K/Akt pathway

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Abstract

Background

Posterior capsule opacification (PCO) represents a major challenge in the postoperative management of cataract patients. Spreading, migration and contraction of residual human lens epithelial cells play a pivotal role in the pathogenesis of PCO. Therefore, we analyzed the effect of the alkylphosphocholine (APC) erufosine on these cellular features as well as on PI3K/Akt, a crucial pathway in PCO pathogenesis.

Methods

Human lens epithelial cells were cultured under standard cell culture conditions. Cell spreading was analyzed on fibronectin-coated wells and chemokinetic migration was assessed by time-lapse microscopy. For evaluation of cell-mediated collagen matrix contraction, the cells were seeded into collagen gels and incubated with an APC in different non-toxic concentrations before the surface area was measured on day 6. The activity of PI3K/Akt was assessed by an ELISA kit after incubation of the cells with different APC concentrations.

Results

Human lens epithelial cell spreading and migration were attenuated by APCs as follows: 7 % spreading, 48 % migration (0.1 μM APC), and 32 % spreading, 68 % migration (1.0 μM APC). APC concentrations of 0.1 μM reduced collagen gel diameter by 5 %, and 1.0 μM by less than 1 %, compared to untreated, cell-populated gels that resulted in a cell diameter contraction of 36 %. PI3K was downregulated in a concentration-dependent manner.

Conclusions

The crucial cellular features of PCO pathogenesis are attenuated by the APC erufosine via downregulation of the PI3K pathway. Thus, erufosine might become a valuable tool for pharmacologic PCO prophylaxis in the future.

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Conflict of Interest

The authors declare that they have no conflicts of interest relevant to this work.

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Authors and Affiliations

  1. Department of Ophthalmology, Ludwig-Maximilians-University, Mathildenstrasse 8, 80336, Munich, Germany

    R. Liegl, C. Wertheimer, M. Kernt, A. Kampik & K. H. Eibl-Lindner

  2. Experimental Surgery and Regenerative Medicine, Department of Surgery, Ludwig-Maximilians-University, Munich, Germany

    D. Docheva

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  1. R. Liegl
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  2. C. Wertheimer
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  3. M. Kernt
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  4. D. Docheva
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Correspondence to K. H. Eibl-Lindner.

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Liegl, R., Wertheimer, C., Kernt, M. et al. Attenuation of human lens epithelial cell spreading, migration and contraction via downregulation of the PI3K/Akt pathway. Graefes Arch Clin Exp Ophthalmol 252, 285–292 (2014). https://doi.org/10.1007/s00417-013-2524-z

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  • DOI: https://doi.org/10.1007/s00417-013-2524-z

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