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Updated: Nov 1, 2025

Preparation and Culture of Rat Lens Epithelial Explants for Studying Terminal Differentiation
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Preparation and Culture of Rat Lens Epithelial Explants for Studying Terminal Differentiation

Published on: September 22, 2009

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Transforming growth factor-β2-mediated mesenchymal transition in lens epithelial cells is repressed in the absence of

Mi-Hyun Nam1, Mina B Pantcheva1, Johanna Rankenberg1

  • 1Sue Anschutz-Rodgers Eye Center and Department of Ophthalmology, School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, U.S.A.

The Biochemical Journal
|June 18, 2021
PubMed

Insights

The receptor for advanced glycation end products (RAGE) is crucial for transforming growth factor-β2 (TGFβ2)-induced epithelial to mesenchymal transition (EMT) in lens epithelial cells. Targeting RAGE may offer a new therapeutic approach for secondary cataracts.

Area of Science:

  • Ophthalmology
  • Cell Biology
  • Molecular Biology

Background:

  • Secondary cataracts are often associated with fibrosis driven by transforming growth factor-β2 (TGFβ2)-induced epithelial to mesenchymal transition (EMT) in lens epithelial cells (LECs).
  • The role of the receptor for advanced glycation end products (RAGE) in this process remains unclear.

Purpose of the Study:

  • To investigate the involvement of RAGE in TGFβ2-mediated EMT in LECs.
  • To explore RAGE as a potential therapeutic target for secondary cataracts.

Main Methods:

  • Utilized RAGE knockout mice and wild-type mice for comparative studies of LECs.
  • Administered TGFβ2 to LECs and analyzed EMT markers, Smad signaling, and IL-6 levels.
  • Treated human LECs with a RAGE inhibitor (FPS-ZM1) and assessed TGFβ2-induced responses.
  • Examined α-smooth muscle actin (α-SMA), fibronectin (FN), and integrin β1 expression in mouse lenses.

Main Results:

  • TGFβ2 failed to induce EMT in LECs from RAGE knockout mice, unlike in wild-type mice.
  • RAGE deficiency attenuated TGFβ2-mediated Smad signaling and IL-6 production in LECs.
  • Inhibition of RAGE in human LECs reduced TGFβ2-induced Smad signaling and EMT.
  • RAGE knockout lenses showed no elevation of α-SMA, FN, and integrin β1 after fiber cell removal, unlike wild-type lenses.

Conclusions:

  • TGFβ2-mediated EMT in LECs is dependent on RAGE signaling.
  • RAGE plays a significant role in the fibrotic processes associated with secondary cataracts.
  • Targeting RAGE presents a promising therapeutic strategy for preventing or treating secondary cataracts.
Keywords:
RAGETGFβ2epithelial to mesenchymal transitionlens epithelial cellsα-smooth muscle actin

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