July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
EGF potentiates TGFβ-induced epithelial-mesenchymal transition (EMT) in lens epithelial cells by enhancing EGFR signaling
Author Affiliations & Notes
  • Daisy Shu
    Clinical Ophthalmology and Eye Health, University of Sydney, Sydney, New South Wales, Australia
    Save Sight Institute, Sydney, New South Wales, Australia
  • Frank J Lovicu
    Clinical Ophthalmology and Eye Health, University of Sydney, Sydney, New South Wales, Australia
    Save Sight Institute, Sydney, New South Wales, Australia
  • Footnotes
    Commercial Relationships   Daisy Shu, None; Frank Lovicu, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 1202. doi:
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      Daisy Shu, Frank J Lovicu; EGF potentiates TGFβ-induced epithelial-mesenchymal transition (EMT) in lens epithelial cells by enhancing EGFR signaling. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1202.

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

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Abstract

Purpose : Epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) plays a crucial role in the pathogenesis of anterior subcapsular cataract (ASC) and posterior capsular opacification (PCO). While transforming growth factor beta (TGFβ) is a potent inducer of EMT in the lens, studies in cancer research have shown that the effects of TGFβ can be augmented by the addition of epidermal growth factor (EGF). The aim of the present study was to investigate the combined effect of TGFβ and EGF in the lens to elucidate the involvement of EGFR (epidermal growth factor receptor)-signaling in TGFβ-induced EMT in LECs.

Methods : Lens epithelial explants from 21-day-old Wistar rats were treated with either 200 pg/ml TGFβ2, 5 ng/ml EGF, or a combination of these, with or without a 2-hour pre-treatment with 50 nM PD153035 (EGFR inhibitor). Expression of β-catenin, alpha-smooth muscle actin (α-SMA), tropomyosin (isoforms 1.6-1.9; CGβ6 Ab) and downstream signaling molecules, including phosphorylated EGFR, Smad2/3 and MAPK/ERK1/2 were determined using immunofluorescence and/or western blotting.

Results : The combined treatment of TGFβ2 and EGF resulted in a more dramatic morphological elongation and transdifferentiation of LECs into myofibroblastic cells compared to TGFβ2 alone. The addition of EGF augmented the expression levels of α-SMA and tropomyosin compared to TGFβ2 alone. Treatment with EGF alone did not induce EMT and did not upregulate mesenchymal markers. Treatment with TGFβ2 alone upregulated the phosphorylation of Smad2/3, ERK1/2 and EGFR signaling. Interestingly, inhibition of EGFR-signaling using PD153035 inhibited TGFβ2-induced EMT by blocking the upregulation of α-SMA and tropomyosin and retaining β-catenin labeling to the cell membrane.

Conclusions : Our findings demonstrate that TGFβ2 cooperates synergistically with EGF to enhance EMT in LECs. Moreover, as TGFβ2 alone can transactivate EGFR signaling, and EGFR-signaling is required for TGFβ activity, we reveal a novel positive feedback mechanism in the pathogenesis of ASC and PCO. Hence, targeting both TGFβ2 and EGFR activity may be a more efficacious strategy in the pharmacological treatment of cataract.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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