March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Inhibiton Of Human Lens Epithelial Cell Contraction By Alkylphosphocholines For PCO Prophylaxis And Downregulation Of The PI3K Pathway
Author Affiliations & Notes
  • Raffael Liegl
    Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany
  • Marcus Kernt
    Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany
  • Armin Wolf
    Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany
  • Daniel Kook
    Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany
  • Christos Haritoglou
    Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany
  • Anselm Kampik
    Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany
  • Kirsten H. Eibl-Lindner
    Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany
  • Footnotes
    Commercial Relationships  Raffael Liegl, None; Marcus Kernt, None; Armin Wolf, None; Daniel Kook, None; Christos Haritoglou, None; Anselm Kampik, None; Kirsten H. Eibl-Lindner, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 6909. doi:
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      Raffael Liegl, Marcus Kernt, Armin Wolf, Daniel Kook, Christos Haritoglou, Anselm Kampik, Kirsten H. Eibl-Lindner; Inhibiton Of Human Lens Epithelial Cell Contraction By Alkylphosphocholines For PCO Prophylaxis And Downregulation Of The PI3K Pathway. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6909.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : As small molecules with an amphiphilic chemical structure, alkylphosphocholines (APCs) can be used as coating agents for intraocular lenses for PCO (posterior capsule opacification) prophylaxis. So far, it has not been studied if these agents are suitable for prophylaxis of human lens capsular contraction as a severe form of PCO. This preclinical study focuses on the evaluation of these substances to inhibit human lens epithelial cell induced contraction of collagen type I matrices in vitro and their effect on PI3K, a crucial pathway in lens cell migration .

Methods: : Human lens epithelial cells (HLE-B3) were cultured under standard cell culture conditions in Eagle’s Modified essential Medium in the presence of 10 % fetal calf serum (FCS). To mimic the more physiologic conditions in the human anterior chamber after cataract surgery, cells were gradually sub cultured in medium containing a maximum serum concentration of 3 % FCS only. HLE-B3 cells were then seeded in collagen gels in a 24-well plate and were incubated with APCs in different non-toxic concentrations, as evaluated previously. After 72 hours, the medium was changed and the collagen gels were incubated for another 3 days before the surface area was measured on day 6. The collagen contraction assay was performed in duplicate and repeated three times. The activity of PI3K was measured using an ELISA kit (echelon) after incubation of HLE-B3 cells in different concentrations.

Results: : Human lens epithelial cells are able to contract collagen type I gels in vitro and can be used as an in vitro model to study the cellular events as seen in human lens capsular contraction. Alkylphosphocholines inhibit collagen type I contraction induced by human lens epithelial cells over 6 days in the presence of 3 % FCS. APC concentrations of 0,01 µM are able to reduce collagen gel contraction by 13 %, while a concentration of 0,1 µM leads to an inhibition of matrix cell contraction by 31%. PI3K was down-regulated in a concentration dependent manner: An APC concentration of 0,5µM led to a decrease in PI3K activity of 50% while 1,0µM decreased PI3K activity by almost 90%.

Conclusions: : APCs are suitable for prophylaxis of human lens epithelial cell contraction in cell-populated collagen type I matrices and downregulates PI3K in a concentration dependent manner. The effect lasts over 6 days in this in vitro model and is non-toxic for the cells. Thus, APC-coated intraocular lenses might also inhibit contraction of the human lens capsule.

Keywords: posterior capsular opacification (PCO) • cataract • intraocular lens 
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