Nox4-mediated ROS production is involved, but not essential for TGFβ-induced lens EMT leading to cataract

S. J. Das, T. F.L. Wishart, K. Jandeleit-Dahm, F. J. Lovicu

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The reactive oxygen species (ROS) producing enzyme, NADPH oxidase 4 (Nox4), is upregulated in response to TGFβ in lens epithelial cells in vitro, and its selective inhibition was shown to block aspects of TGFβ-induced epithelial-mesenchymal transition (EMT). In the present in situ study we validate the role(s) of Nox4 in TGFβ-induced lens EMT leading to anterior subcapsular cataract (ASC) formation. Mice overexpressing TGFβ in the lens, that develop ASC, were crossed to Nox4-deficient mice. When comparing mice overexpressing TGFβ in lens, to mice that were also deficient for Nox4, we see the delayed onset of cataract, along with a delay in EMT protein markers normally associated with TGFβ-induced fibrotic cataracts. In the absence of Nox4, we also see elevated levels of ERK1/2 activity that was shown to be required for TGFβ/Smad2/3-signaling. qRT-PCR revealed upregulation of Nox2 and its regulatory subunit in TGFβ-overexpressing lens epithelial cells devoid of Nox4. Taken together, these findings provide an improved platform to delineate putative Nox4 (and ROS) interactions with Smad2/3 and/or ERK1/2, in particular in the development of fibrotic diseases, such as specific forms of cataract.

Original languageEnglish
Article number107918
Number of pages15
JournalExperimental Eye Research
Publication statusPublished - Mar 2020


  • Anterior subcapsular cataract
  • Cataract
  • Epithelial-mesenchymal transition (EMT)
  • ERK1/2
  • Fibrosis
  • Lens
  • Myofibroblast
  • Nox2
  • Nox4
  • ROS
  • Smad
  • Transforming growth factor-beta (TGFβ)

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